Polymeric surface having reduced biomolecule adhesion to thermoplastic articles

Abstract

A substrate having a treated contact surface is described, comprising a carbon or silicon compound containing 1 to 30 atomic percent oxygen, 0.1 to 30 atomic percent nitrogen, or both, when each is measured by XPS. The treated contact surface has a biomolecule recovery percentage greater than the biomolecule recovery percentage of the surface prior to treatment according to the present method.

Description

Technology Field

[0001] This specification claims priority to U.S. Provisional Application No. 62 / 320,246, filed April 8, 2016. The full text of such application is incorporated herein by reference to provide continuity of the content of this disclosure.

[0002] The present invention generally relates to a surface of a plastic substrate, or a surface modification (sometimes referred to as a contact surface in this disclosure), in which biomolecule attachment to the surface is reduced. More particularly, the present invention relates to a plastic substrate, for example, an item of medical device or laboratory ware, in which protein attachment to the surface is reduced. Background Technology

[0003] In the testing of blood, biomolecules, and blood analytes, it is desirable to minimize the adsorption and binding of biomolecules onto plastic items used with these biological materials. Plastic microwell plates, chromatography vials, and other containers used for preparing and transferring samples, as well as pipettes (sometimes spelled "pipet"), pipette tips, centrifuge tubes, microscope slides, and other types of laboratory supplies (also known as labware), typically have hydrophobic surfaces that readily adsorb biomolecules such as proteins, DNA, and RNA. The surfaces of these and other types of laboratory supply components made of polymeric plastics can cause the binding of biomolecule samples. Accordingly, the aim is to provide surfaces on plastic laboratory supplies and other items that come into contact with biological materials that reduce the attachment of a wide range of biomolecules.

[0004] The present invention also relates to the technical field of manufacturing coated containers for chemical, biochemical, medical, and / or biological uses. Such methods and systems are essential in various applications including medical diagnosis, medical treatment, food and beverage testing, food and beverage packaging, environmental monitoring, manufacturing quality control, drug development, and scientific research.

[0005] In vitro and analytical tests are typically performed on special-purpose laboratory glassware and plastic products to contain and place test samples. Traditionally, glassware has been and continues to be used, but glassware is easily broken, very expensive, causes particulate issues, results in heavy metal extracts, and can cause aggregation of proteins and other biological materials.

[0006] Some of these problems can be resolved by replacing glass products with injection-molded plastic products. In particular, plastic products are desirable in biological fields such as pharmaceuticals, medical research, drug development, and scientific research due to the numerous issues associated with glass products. While plastic products address some of the problems associated with glass products, they also introduce specific issues. These can lead to non-specific binding of biomolecules to plastic products as well as non-specific adsorption of biomolecules onto them. Furthermore, plastic products may contain leachable substances, which prevents their use or renders them undesirable for many types of in vitro and analytical laboratory tests.

[0007] In addition, pipettes, pipette tips, and centrifuge tubes are other types of laboratory supplies used to prepare and transport samples and reagent solutions, and these can also be made of glass or plastic. In the testing of blood, biomolecules, and blood analytes, it is desirable to minimize biomolecule adsorption and non-specific biomolecule binding to plastic products. Furthermore, in in vitro and analytical tests, it is desirable to minimize biomolecule adsorption and non-specific biomolecule binding to plastic products. Plastic microwell plates, vials, and other containers used to prepare and transport samples, as well as pipettes, pipette tips, centrifuge tubes, and other types of laboratory supplies with hydrophobic surfaces, readily adsorb biomolecules such as proteins, DNA, and RNA. The surfaces of these and other types of laboratory supply components made of polymerizable plastics can cause non-specific binding of samples. The surfaces of these and other types of laboratory supply components made of glass can cause particulate issues, contain heavy metal extracts, and lead to the aggregation of proteins and other biomolecules. Conventional hydrophilic coatings, including polyethylene glycol (PEG) and zwitterionic polymerizable coatings, have been found to provide excellent biomolecular adsorption performance. Many of these polymerizable coatings are not covalently bonded to the surface of the article and have the potential to migrate (dissolve, disperse) into the fluid payload, thereby causing interference with assay tests and / or exposing the plastic surface to protein surface adsorption, which limits their utility. A polymerizable coating covalently bonded to the surface of the article does not have the potential to migrate (dissolve, disperse) into the fluid payload, thus eliminating these sources of interference with assay tests. Furthermore, a covalently bonded polymerizable coating prevents the movement of the polymerizable surface coating, thereby preventing undesirable exposure of the article surface.

[0008] Accordingly, there is a need for a covalently bonded polymerizable coating for the surfaces of plastic laboratory supplies such as microwell plates, vials, other containers, pipettes, pipette tips, and centrifuge tubes, which inhibits the adsorption of biomolecules onto the plastic surface. Similarly, there is a need for a bonded polymerizable coating for the surfaces of plastic laboratory supplies such as microwell plates, vials, other containers, pipettes, pipette tips, and centrifuge tubes, which prevents undesirable exposure of the plastic surface by hindering the movement of the polymerizable surface coating.

[0009] A critical consideration in the manufacturing packaging of regulated products, such as pharmaceuticals, is ensuring that there are substantially no contaminants present in the medicine contained within the packaging material. Accordingly, the processes of manufacturing pharmaceutical packaging and filling it with products are typically carried out under cleanroom conditions.

[0010] One potential source of contamination is particulate matter. Particulate contamination can originate from various sources, which can generally be divided into two categories: (1) intrinsic contaminants; and (2) extrinsic contaminants. Intrinsic contaminants are product and process-related particulates, e.g., laser etching residue, filter media, cleanroom uniform fibers, rubber and plastic particles from filter housings, and needle shields. Extrinsic contaminants originate from sources unrelated to the product or process, such as hair, skin cells, pollen, clothing fibers, salt, and soil.

[0011] While filtration systems and manufacturing practices can limit the number of surface and airborne particulates in the areas where containers are manufactured or filled, these do not always reduce the number of particulates on the container surface to an acceptable level. One particular challenge arises from the electrostatic charge of manufactured plastic containers, which tends to attract charged particles. Even if the number of airborne / surface particulates is relatively low, plastic containers with strong electrostatic charges can attract particulate contaminants and cause them to adhere to the container.

[0012] Attempted solutions to these problems include the use of antistatic additives for polymers, e.g., ethoxylated alkylamines, ethoxylated alkyl amides, glycerol stearates, fatty acid esters, esters or ethers of polyols, and sodium alkyl sulfons. The amount of these additives in the polymer typically varies from 0.1 wt% to 3 wt%. While these additives are somewhat effective in reducing the electrostatic charge of plastic articles containing them, the additives are mobile within the polymer matrix and tend to bloom on the surface. Additives blooming on the surface can contaminate the surface and the contents of containers made from the polymer with these additives, particularly liquid contents.

[0013] Accordingly, there is a demand for plastic articles treated to reduce their static charge without using conventional antistatic additives, which can themselves be a source of contamination. Likewise, there is a demand for methods to treat plastic articles to reduce their static charge without using conventional antistatic additives. Additionally, many of these coatings require fluid-phase chemistry involving reactants and solvents. The problem to be solved

[0014] An embodiment of the present invention is a polymerizable substrate essentially comprising a contact surface and an internal portion. The contact surface comprises 1 to 30 atomic percent oxygen atoms, 0 to 30 atomic percent nitrogen atoms, and 70 to 99 atomic percent carbon atoms. The atomic percent values ​​are measured by X-ray photoelectron spectroscopy (XPS).

[0015] Another aspect of the present invention is a method for providing a polymerizable article having a contact surface containing carbon and forming any of the claims by treating the contact surface. The contact surface is treated with a conversion plasma containing water vapor and oxygen. The treatment is performed under conditions effective for forming a converted surface having a biomolecule recovery percentage greater than the biomolecule recovery percentage of the contact surface before treating the contact surface with the conversion plasma. The biomolecule recovery percentage is determined for an aqueous protein dispersion having a concentration of 0.01 nM to 1.4 nM, optionally 0.05 nM to 1.4 nM, and optionally 0.1 nM to 1.4 nM, in contact with the converted surface.

[0016] Another aspect of the present invention resolves the drawbacks of conventional coatings and coated containers by providing a covalently bonded polymerizable zwitterionic monolayer or an epoxy-modified zwitterionic-containing copolymer monolayer capable of providing excellent inhibition of surface absorption of biomolecules and inhibition of non-specific binding between the surface and biomolecules without concern for polymer dissolution / dispersion in a fluid medium. Embodiment (i) provides a reaction of a siloxane-functional polymer containing surface-bonded hydroxyl groups and zwitterionic functionality. Embodiment (ii) provides a hydroxylated plastic or SiO₂ to ensure covalent surface bonding. x - Provides a reaction between a coated glass surface and an epoxy-modified zwitterion-containing copolymer.

[0017] The present invention relates to hydroxylated plastic or SiOx - Coated glass surface, and in embodiment (i), condensation (water or volatile alcohol loss (e.g., surface SiOH + polymer (zwitterion-siloxane-Si(OR)) x ) → between zwitterion-siloxane copolymers arising from surface SiO-Si(polymer (zwitterion-siloxane))) + ROH), or in embodiment (ii), hydroxylated plastic or SiO to form an epoxy-modified zwitterion-containing copolymer monolayer. x - It utilizes the formation of covalent bonds between epoxy-modified zwitterionic-containing copolymers resulting from the functionalization of the coated glass surface into a silyl amine coupling agent, followed by further functionalization into a zwitterionic epoxy copolymer.

[0018] The present invention generally relates to a method for coating the surface of a container, such as laboratory supplies and containers used for purposes of analytical chemistry, medical research, drug development, and scientific research (e.g., chromatography vials, microplates, pipettes, pipette tips, centrifuge tubes, etc.), or other containers and / or surfaces that come into contact with biomolecule-containing materials, such as beakers, round-bottom flasks, Erlenmeyer flasks, graduated cylinders, etc. Biomolecules may include, for example, simple biomolecules (e.g., nucleotides, amino acids, monosaccharides, and fatty acids), nucleic acid molecules, polynucleotides, polypeptides, polysaccharides, lipids, steroids, or their conjugates (e.g., glycoproteins, lipoproteins, glycolipids, DNA-protein conjugates), antibodies, receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, antibody fusion proteins, as well as cells, viruses, and bacteria. A preferred application of the present invention is, for example, to have a non-parenteral container, but a non-parenteral container processed according to the process disclosed herein is also within such a range.

[0019] More specifically, the present invention relates to a covalently bonded (i) polymerizable zwitterionic monolayer or (ii) epoxy-modified zwitterionic-containing copolymer monolayer known to exhibit excellent resistance to adsorption and / or non-specific binding of non-specific biomolecules, such as proteins, in a laboratory setting, wherein the zwitterionic deposition is performed using a multi-step process. In this invention, a commercially viable process providing both low cost and product performance has been developed based on the concept of a unique biomolecule, e.g., a protein, and the adsorption resistance properties of a covalently bonded (i) polymerizable zwitterionic monolayer coating or (ii) epoxy-modified zwitterionic-containing copolymer monolayer. Covalently bonded (i) polymerizable zwitterionic monolayer coatings or (ii) epoxy-modified zwitterionic-containing copolymer monolayer coatings to these products improve their sample-contact characteristics to configure them to come into contact with biomolecule-containing samples, such as proteins or other peptide or polypeptide samples, for example, to provide surfaces having non-binding or low-binding properties. For example, the present invention considers a method of coating the surface of these products with a covalently bonded (i) polymerizable zwitterionic monolayer coating or (ii) epoxy-modified zwitterionic-containing copolymer monolayer coating to obtain a surface coating resistant to non-specific biomolecule adsorption and / or non-specific binding. Such covalently bonded (i) polymerizable zwitterionic monolayer coatings or (ii) epoxy-modified zwitterionic-containing copolymer monolayer coatings have desirable properties when used as coatings for surfaces in contact with biomolecule-containing samples.

[0020] Additionally, in one embodiment, the present invention is a method for reducing the electrostatic charge of a plastic container. The present invention provides a covalently bonded (i) polymerizable zwitterionic monolayer coating or (ii) epoxy-modified zwitterionic-containing copolymer monolayer capable of providing excellent inhibition of biomolecular adsorption and inhibition of non-specific biomolecular surface binding without concern for polymer dissolution / dispersion in a fluid medium, comprising a siloxane-functional polymer containing zwitterionic functionality and (i) surface-bonded hydroxyl groups or (ii) hydroxylated plastic or SiO₂ x - It utilizes the reaction of the coated glass surface. The coating reduces the electrostatic charge of the container compared to a reference container that is essentially identical to the container except that the reference container is uncoated.

[0021] The present invention utilizes a sequential reaction.

[0022] In embodiment (i), these sequential reactions are (1) hydroxy-modified or SiO x The method comprises using a plasma-modified surface and subsequently forming a zwitterion-siloxane copolymer resulting from condensation (2) the loss of water or volatile alcohol (e.g., surface SiOH + polymer (zwitterion-siloxane-Si(OR)x) → surface SiO-Si (polymer (zwitterion-siloxane))) + ROH). In certain embodiments, the hydroxyl-functional surface may be formed (A) from an O2 / plasma reaction, for example, on a carbon-based polymer surface (AC), or a C-OH moiety, or on a silicon-based (SiO2 or silicon) surface (ASi), a Si-OH moiety. Additionally, the hydroxyl-functional surface may be (B) inherent in the initial surface, for example, the polymer, for example, polyvinyl alcohol (PVOH) or the silicon-based polymer surface (SiO2 or silicon). Accordingly, the O2 / plasma surface preparation method may be selective when hydroxyl moiety is present on the surface.

[0023] In embodiment (ii), these sequential reactions are (1) hydroxy-modified or SiO x A plasma-modified surface is formed, and subsequently, (2) a hydroxy-modified or SiO2 surface is formed. x (3) Forming an amine-modified surface by reacting a plasma-modified surface with a silyl amine coupling agent, and then forming an amine linked by the condensation of the amine-modified surface with an epoxy-modified zwitterion-containing copolymer.

[0024] The coating can be both polymerizable and hydrophilic (binding water to ionic moiety), providing a durable stereochemical and bound-water barrier against biomolecule adsorption and non-specific biomolecule binding on plastic surfaces.

[0025] Although the zwitterionic layer may be thinner than the polymerizable zwitterionic coating, solvent coating methods, i.e., evaporation, may cause non-uniform coating, which can result in (a) optically observable non-uniformity, (b) a discarded coating (a coating thickness greater than required / desired), and the material of the present invention must provide good biomolecular adsorption and / or binding inhibition.

[0026] A list of relevant non-limiting patents includes U.S. Patents No. 6,068,884 and 4,844,986 and U.S. Publication Applications No. 20060046006, 20040267194, 20140004022 and 20130209766.

[0027] All references cited in this document are incorporated herein by reference in their entirety.

[0028] The present invention provides a method for providing a non-specific biomolecule adsorption and / or binding-resistant coated surface exhibiting low- or non-binding and / or low- or non-adsorption of biomolecules.

[0029] An embodiment of the method (i) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing O2 near the surface of the substrate; (d) generating a plasma from the gas to thereby form a hydroxyl-functional substrate surface and optionally heating the substrate; (e) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (f) reacting the hydroxyl-functional surface with the at least one zwitterionic copolymer and optionally heating the substrate; (g) optionally waiting; (h) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0030] An embodiment of the method (ii) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing O2, optionally containing argon, and optionally containing nitrogen near the surface of the substrate; (d) generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) optionally providing a copolymer solution containing a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) reacting the copolymer with the amine-modified substrate and optionally heating the substrate; (h) optionally waiting. (i) a step of removing the copolymer, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0031] Either embodiment (i) or embodiment (ii) provides a method for providing a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface exhibiting low- or non-binding of biomolecules and / or low- or non-adsorption of biomolecules.

[0032] Embodiment (i) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing an organosilicon precursor and optionally O2 near the surface of the substrate; (d) generating a plasma from the gas and thereby forming a hydroxyl-functional substrate surface; (e) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (f) reacting the hydroxyl-functional surface with at least one zwitterionic copolymer and optionally heating the substrate; (g) optionally waiting; (h) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0033] Example (ii) is (a) SiO x- A step of providing a substrate which is a coated glass surface reaction chamber; (b) a step of forming a vacuum in the reaction chamber; (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen; (d) a step of generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) a step of providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) a step of optionally providing a copolymer solution containing a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) a step of reacting the copolymer with the amine-modified substrate and optionally heating the substrate; (h) a step of removing the copolymer solution; (i) a step of optionally drying a coated surface that is resistant to non-specific biomolecule adsorption and / or non-specific binding; and (j) optionally, a step of heating the surface and thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0034] Embodiment (i) is a method for providing a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface exhibiting low or non-binding of biomolecules and / or low or non-adsorption of biomolecules, comprising: (a) providing a substrate having a hydroxyl-functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl-functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (d) optionally waiting; (e) a method comprising the step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0035] Embodiment (i) provides a method for covalently bonding a zwitterionic copolymer to a prepared substrate surface.

[0036] Embodiment (ii) comprises at least one silylamine coupling agent, 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, bis(triethoxysilylpropyl)amine, bis(trimethoxysilylpropyl)amine,Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, The present invention provides a method selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0037] Embodiment (ii) comprises at least one copolymerizable zwitterionic monomer including 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,The present invention provides a method selected from the group consisting of hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0038] Embodiment (ii) comprises at least one copolymerizable epoxy monomer, glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, and (oxiran-2-yl)methyl A method is provided that is selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0039] Embodiment (ii) provides a method in which an epoxy-modified zwitterionic copolymer is covalently bonded to an amine-modified substrate.

[0040] In either embodiment (i) or embodiment (ii), the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, methylene chloride, 1,2-dichloroethane and combinations thereof.

[0041] Either embodiment (i) or embodiment (ii) provides a method in which a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface has reduced biomolecule binding compared to an untreated substrate.

[0042] Either embodiment (i) or embodiment (ii) provides a method in which the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0043] Either embodiment (i) or embodiment (ii) provides a method in which the substrate is the surface of the container.

[0044] Either embodiment (i) or embodiment (ii) provides a method in which the container is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask.

[0045] Embodiment (i) is an alternative comprising: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing an organosilicon precursor and optionally O2 near the surface of the substrate; (d) generating a plasma from the gas and thereby forming a hydroxyl-functional substrate surface; (e) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (f) reacting the hydroxyl-functional surface with the at least one zwitterionic copolymer and optionally heating the substrate; (g) optionally waiting; (h) Provides a non-specific biomolecule adsorption and / or non-specific binding-resistant coated substrate prepared by the step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0046] Embodiment (i) further provides a non-specific biomolecule adsorption and / or non-specific binding-resistant coated substrate prepared by the steps of: (a) providing a substrate having a hydroxyl-functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl-functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (d) optionally waiting; and (e) removing the copolymer solution and optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally, heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0047] Embodiment (ii) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing O2 in the vicinity of the substrate surface, optionally containing argon, and optionally containing nitrogen; (d) generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) optionally providing a copolymer solution containing a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) reacting the copolymer with the amine-modified substrate and optionally heating the substrate; A non-specific biomolecule adsorption and / or non-specific binding-resistant coated substrate is provided, prepared by the steps of removing a copolymer solution, optionally drying a surface coated with non-specific biomolecule adsorption and / or binding resistance, optionally heating the surface, and thereby forming a substrate coated with non-specific biomolecule adsorption and / or binding resistance.

[0048] Embodiment (i) provides a substrate coated with a non-specific biomolecule adsorption and / or binding resistance coating having reduced biomolecule binding compared to a non-treated substrate. The biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0049] Example (ii) is (a) SiOx - A step of providing a substrate which is a reaction chamber coated with a glass surface; (b) a step of forming a vacuum in the reaction chamber; (c) a step of providing a gas containing O2, optionally containing argon, and optionally containing nitrogen near the surface of the substrate; (d) a step of generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) a step of providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) a step of providing a copolymer solution containing a solvent in the presence of an optional polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) a step of reacting the copolymer with the amine-modified substrate and optionally heating the substrate; (h) a step of optionally waiting; (i) a substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance, prepared by the step of removing the copolymer solution, optionally drying the surface coated with non-specific biomolecule adsorption and / or non-specific binding resistance, optionally heating the surface, thereby forming a substrate coated with non-specific biomolecule adsorption and / or binding resistance.

[0050] In embodiment (ii), at least one silylamine coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltriris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, Bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, Bis(triethoxysilylpropyl)amine, Bis(trimethoxysilylpropyl)amine,Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, Selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0051] Embodiment (ii) comprises at least one copolymerizable zwitterionic monomer including 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,Hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; The present invention provides a substrate coated to withstand non-specific biomolecule adsorption and / or non-specific binding, selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), b-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0052] Embodiment (i) provides a non-specific biomolecule adsorption and / or non-specific binding-resistant coated substrate prepared by the steps of: (a) providing a substrate having a hydroxyl functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (d) optionally, waiting; (e) removing the copolymer solution and optionally, drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally, heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0053] Embodiment (i) provides a substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance, wherein a zwitterionic copolymer is covalently bonded to the surface of a prepared substrate.

[0054] At least one copolymerizable epoxy monomer of embodiment (ii) is glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, (oxiran-2-yl)methyl It is selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0055] Either embodiment (i) or embodiment (ii) provides a substrate coated with a non-specific biomolecule adsorption and / or binding resistance coating having reduced biomolecule binding compared to an untreated substrate.

[0056] Either embodiment (i) or embodiment (ii) provides a substrate coated with resistance to adsorption and / or binding of a non-specific biomolecule, wherein the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0057] The present invention provides a substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance, wherein the substrate is the surface of a container.

[0058] The present invention provides a substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance, wherein the container is selected from the group consisting of microplates; centrifuge tubes; pipette tips; cuvettes, microwell plates; ELISA plates; microtiter plates; 96-well plates; and 384-well plates.

[0059] Embodiment (i) is an alternative comprising: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing O2 near the surface of the substrate; (d) generating a plasma from the gas to thereby form a hydroxyl-functional substrate surface and optionally heating the substrate; (e) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers comprising at least one siloxane moiety and at least one zwitterionic moiety; (f) reacting the hydroxyl-functional surface with at least one zwitterionic copolymer and optionally heating the substrate; (g) optionally waiting; (h) Provides a container having at least a portion of an inner surface coated with a non-specific biomolecule adsorption and / or binding resistance coating, prepared by the step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding resistance coating surface, optionally heating the surface, and thereby forming a non-specific biomolecule adsorption and / or binding resistance coating container.

[0060] Embodiment (i) provides, as another alternative, a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding-resistant coating, prepared by the steps of: (a) providing a substrate having a hydroxyl functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (c) optionally waiting; and (d) removing the copolymer solution and optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0061] Embodiment (ii) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing O2 in the vicinity of the substrate surface, optionally containing argon, and optionally containing nitrogen; (d) generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) optionally providing a copolymer solution containing a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) reacting the copolymer with the amine-modified substrate and optionally heating the substrate; (h) optionally waiting. (i) a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding resistance coating, prepared by the step of removing a copolymer solution, optionally drying the surface coated with a non-specific biomolecule adsorption and / or non-specific binding resistance coating, optionally heating the surface, and thereby forming a container coated with a non-specific biomolecule adsorption and / or binding resistance coating.

[0062] Embodiment (i) comprises: (a) providing a substrate in a reaction chamber; (b) forming a vacuum in the reaction chamber; (c) providing a gas containing an organosilicon precursor and optionally O2 near the surface of the substrate; (d) generating a plasma from the gas and thereby forming a hydroxyl functional surface on the surface of the substrate; (e) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (f) reacting the hydroxyl functional surface with the at least one zwitterionic copolymer and optionally heating the substrate; (g) optionally waiting; (h) Provides a container having at least a portion of an inner surface coated with a non-specific biomolecule adsorption and / or binding resistance coating, prepared by the step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding resistance coating surface, optionally heating the surface, and thereby forming a non-specific biomolecule adsorption and / or binding resistance coating container.

[0063] Embodiment (ii) is (a) SiO in the reaction chamber x- A step of providing a substrate having a coated glass surface; (b) a step of forming a vacuum in a reaction chamber; (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen; (d) a step of generating a plasma from the gas to thereby form a prepared substrate surface and optionally heating the substrate; (e) a step of providing an amine-modified substrate by providing a vapor containing at least one silylamine coupling agent; (f) a step of providing a copolymer solution containing a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer; (g) a step of reacting the copolymer with the amine-modified substrate and optionally heating the substrate; (h) an optional step of waiting; (i) a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding resistance coating, prepared by the step of removing a copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding resistance coated surface, optionally heating the surface, and thereby forming a container coated with a non-specific biomolecule adsorption and / or binding resistance coating.

[0064] Embodiment (i) provides a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding-resistant coating, prepared by the steps of: (a) providing a substrate having a hydroxyl functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers comprising at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (c) optionally waiting; and (d) removing the copolymer solution and optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally, heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0065] Embodiment (i) alternatively provides a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding-resistant coating, prepared by the steps of: (a) providing a substrate having a hydroxyl functional surface; (b) providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety; (c) reacting the hydroxyl functional surface with the at least one zwitterionic copolymer and optionally, heating the substrate; (c) optionally waiting; and (d) removing the copolymer solution and optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally, heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0066] The present invention provides a container coated with non-specific biomolecule adsorption and / or non-specific binding resistance, wherein a zwitterionic copolymer is covalently bonded to the surface of a prepared substrate.

[0067] Embodiment (ii) comprises at least one silylamine coupling agent, 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, bis(triethoxysilylpropyl)amine, bis(trimethoxysilylpropyl)amine,Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, The present invention provides a non-specific biomolecule adsorption and / or binding-resistant coated container selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0068] Embodiment (ii) comprises at least one copolymerizable zwitterionic monomer including 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,Hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; The present invention provides a non-specific biomolecule adsorption and / or non-specific binding resistant coated container selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), b-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0069] Embodiment (ii) comprises at least one copolymerizable epoxy monomer, glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, and (oxiran-2-yl)methyl A non-specific biomolecule adsorption and / or binding resistant coated container is provided, selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0070] Either embodiment (i) or embodiment (ii) provides a non-specific biomolecule adsorption and / or binding-resistant coated container having reduced biomolecule binding compared to an untreated substrate.

[0071] Either embodiment (i) or embodiment (ii) provides a non-specific biomolecule adsorption and / or binding-resistant coated container in which the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0072] Either embodiment (i) or embodiment (ii) provides a non-specific biomolecule adsorption and / or non-specific binding resistant coated container, the container being selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette; a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; and a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask.

[0073] Embodiment (i) is a zwitterionic copolymer comprising (3-acryloxypropyl)trimethoxysilane; methacryloxypropyltrimethoxysilane; n-(3-acryloxy-2-hydroxypropyl)-3-aminopropyltriethoxysilane; o-(methacryloxyethyl)-n-(triethoxysilylpropyl)urethane; n-(3-methacryloxy-2-hydroxypropyl)-3-aminopropyltriethoxysilane; methacryloxymethyltriethoxysilane; methacryloxymethyltrimethoxysilane; methacryloxypropyltriethoxysilane; (3-acryloxypropyl)methyl-dimethoxysilane; (methacryloxymethyl)methyl-dimethoxysilane; (methacryloxymethyl)methyl-dimethoxysilane; methacryloxypropylmethyldimethoxysilane; It comprises at least one siloxane moiety selected from the group consisting of methacryloxypropyl dimethyl ethoxysilane; methacryloxypropyl dimethyl methoxysilane; and combinations thereof; At least one zwitterion moiety comprises 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (including MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate,2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate,2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate, hexahydrophthalate monohydroxyethyl(meth)acrylate, omega-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; The present invention provides a compound selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0074] A method for providing a non-specific biomolecule adsorption and / or binding-resistant coated surface exhibiting low- or non-binding of biomolecules and / or low- or non-adsorption of biomolecules according to embodiment (i),

[0075] (a) a step of providing a substrate to a reaction chamber;

[0076] (b) a step of forming a vacuum in the reaction chamber;

[0077] (c) a step of providing a gas containing O2 near the surface of the substrate;

[0078] (d) a step of generating plasma from a gas, thereby forming a hydroxyl-functional substrate surface, and optionally, heating the substrate;

[0079] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises a moiety comprising at least one siloxane moiety and at least one zwitterionic moiety;

[0080] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0081] (g) Optionally waiting step;

[0082] (h) A method is described comprising the steps of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0083] Optionally, in embodiment (i), the method

[0084] (a) a step of providing a substrate to a reaction chamber;

[0085] (b) a step of forming a vacuum in the reaction chamber;

[0086] (c) a step of providing a gas containing an organosilicon precursor and optionally O2 near the substrate surface;

[0087] (d) a step of generating plasma from a gas and thereby forming a hydroxyl-functional substrate surface;

[0088] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises a moiety comprising at least one siloxane moiety and at least one zwitterionic moiety;

[0089] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0090] (g) Optionally waiting step;

[0091] (h) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0092] Optionally, in implementation example (i), the method

[0093] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0094] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0095] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0096] (d) Optionally waiting step;

[0097] (e) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0098] Optionally, in implementation example (i), the method

[0099] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0100] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0101] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0102] (d) Optionally waiting step;

[0103] (e) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0104] Optionally, in embodiment (i), the zwitterionic copolymer

[0105] (3-Acryloxypropyl) Trimethoxysilane; Methacryloxypropyl Trimethoxysilane; n-(3-Acryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; o-(Methacryloxyethyl)-n-(Triethoxysilylpropyl) Urethane; n-(3-Methacryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; Methacryloxymethyl Triethoxysilane; Methacryloxymethyl Trimethoxysilane; Methacryloxypropyl Triethoxysilane; (3-Acryloxypropyl) Methyl-Dimethoxysilane; (Methacryloxymethyl) Methyl-Diethoxysilane; (Methacryloxymethyl) Methyl-Dimethoxysilane; Methacryloxypropyl Methyl Dimethoxysilane; Methacryloxypropyl Dimethyl Ethoxysilane; At least one siloxane moiety selected from the group consisting of methacryloxypropyldimethyl methoxysilane and combinations thereof; and

[0106] 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (including MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methiacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate,4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, Ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate, hexahydrophthalate monohydroxyethyl(meth)acrylate,It comprises at least one zwitterion moiety selected from the group consisting of omega-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0107] Optionally, in embodiment (i), the zwitterionic copolymer is covalently bonded to the surface of the prepared substrate.

[0108] Optionally, in embodiment (i), the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, methylene chloride, 1,2-dichloroethane and combinations thereof.

[0109] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface has reduced biomolecule binding compared to the untreated substrate.

[0110] Optionally, in embodiment (i), the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0111] Optionally, in embodiment (i), the substrate is the surface of the container.

[0112] Optionally, in embodiment (i), the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask.

[0113] Optionally, in embodiment (i), the substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance is

[0114] (a) a step of providing a substrate to a reaction chamber;

[0115] (b) a step of forming a vacuum in the reaction chamber;

[0116] (c) a step of providing a gas containing O2 near the surface of the substrate;

[0117] (d) a step of generating plasma from a gas, thereby forming a hydroxyl-functional substrate surface, and optionally, heating the substrate;

[0118] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises a moiety comprising at least one siloxane moiety and at least one zwitterionic moiety;

[0119] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0120] (g) Optionally waiting step;

[0121] (h) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0122] Optionally, in embodiment (i), the description is

[0123] (a) a step of providing a substrate to a reaction chamber;

[0124] (b) a step of forming a vacuum in the reaction chamber;

[0125] (c) a step of providing a gas containing an organosilicon precursor and optionally O2 near the substrate surface;

[0126] (d) a step of generating plasma from a gas and thereby forming a hydroxyl-functional substrate surface;

[0127] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises a moiety comprising at least one siloxane moiety and at least one zwitterionic moiety;

[0128] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0129] (g) Optionally, a waiting step;

[0130] (h) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0131] Optionally, in embodiment (i), the description is

[0132] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0133] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers comprising at least one siloxane moiety and at least one zwitterionic moiety;

[0134] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0135] (d) Optionally waiting step;

[0136] (e) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0137] Optionally, in embodiment (i), the description is

[0138] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0139] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0140] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0141] (d) Optionally, a waiting step;

[0142] (e) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0143] Optionally, in embodiment (i), the zwitterionic copolymer

[0144] (3-Acryloxypropyl) Trimethoxysilane; Methacryloxypropyl Trimethoxysilane; n-(3-Acryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; o-(Methacryloxyethyl)-n-(Triethoxysilylpropyl) Urethane; n-(3-Methacryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; Methacryloxymethyl Triethoxysilane; Methacryloxymethyl Trimethoxysilane; Methacryloxypropyl Triethoxysilane; (3-Acryloxypropyl) Methyl-Dimethoxysilane; (Methacryloxymethyl) Methyl-Diethoxysilane; (Methacryloxymethyl) Methyl-Dimethoxysilane; Methacryloxypropyl Methyl Dimethoxysilane; Methacryloxypropyl Dimethyl Ethoxysilane; At least one siloxane moiety selected from the group consisting of methacryloxypropyldimethyl methoxysilane and combinations thereof; and

[0145] 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (including MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methiacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate,4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, Ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate, hexahydrophthalate monohydroxyethyl(meth)acrylate,It comprises at least one zwitterion moiety selected from the group consisting of omega-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0146] Optionally, in embodiment (i), the zwitterionic copolymer is covalently bonded to the surface of the prepared substrate.

[0147] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or binding-resistant coating has reduced biomolecule binding compared to the untreated substrate.

[0148] Optionally, in embodiment (i), the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0149] Optionally, in embodiment (i), the substrate is the surface of the container.

[0150] Optionally, in embodiment (i), the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; and a 384-well plate.

[0151] Optionally, in embodiment (i), a container having an inner surface partially coated with a non-specific biomolecule adsorption and / or binding-resistant coating is

[0152] (a) a step of providing a substrate to a reaction chamber;

[0153] (b) a step of forming a vacuum in the reaction chamber;

[0154] (c) a step of providing a gas containing O2 near the surface of the substrate;

[0155] (d) a step of generating plasma from a gas, thereby forming a hydroxyl-functional substrate surface, and optionally, heating the substrate;

[0156] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0157] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0158] (g) Optionally waiting step;

[0159] (h) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0160] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or binding resistance coating is

[0161] (a) a step of providing a substrate to a reaction chamber;

[0162] (b) a step of forming a vacuum in the reaction chamber;

[0163] (c) a step of providing a gas containing an organosilicon precursor and optionally O2 near the substrate surface;

[0164] (d) a step of generating plasma from a gas and thereby forming a hydroxyl-functional surface on the surface of a substrate;

[0165] (e) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0166] (f) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer, and optionally, heating the substrate;

[0167] (g) Optionally waiting step;

[0168] (h) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0169] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or binding resistance coating is

[0170] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0171] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0172] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0173] (c) Optionally waiting step;

[0174] (d) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0175] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or binding resistance coating is

[0176] (a) a step of providing a substrate having a hydroxyl-functional surface;

[0177] (b) a step of providing a copolymer solution comprising a solvent and at least one zwitterionic copolymer, wherein the at least one zwitterionic copolymer comprises two or more monomers, wherein the at least one zwitterionic copolymer comprises at least one siloxane moiety and at least one zwitterionic moiety;

[0178] (c) reacting a hydroxyl-functionalized surface with at least one zwitterionic copolymer and optionally, heating the substrate;

[0179] (c) Optionally waiting step;

[0180] (d) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated container.

[0181] Optionally, in embodiment (i), the zwitterionic copolymer

[0182] (3-Acryloxypropyl) Trimethoxysilane; Methacryloxypropyl Trimethoxysilane; n-(3-Acryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; o-(Methacryloxyethyl)-n-(Triethoxysilylpropyl) Urethane; n-(3-Methacryloxy-2-Hydroxypropyl)-3-Aminopropyl Triethoxysilane; Methacryloxymethyl Triethoxysilane; Methacryloxymethyl Trimethoxysilane; Methacryloxypropyl Triethoxysilane; (3-Acryloxypropyl) Methyl-Dimethoxysilane; (Methacryloxymethyl) Methyl-Diethoxysilane; (Methacryloxymethyl) Methyl-Dimethoxysilane; Methacryloxypropyl Methyl Dimethoxysilane; Methacryloxypropyl Dimethyl Ethoxysilane; At least one siloxane moiety selected from the group consisting of methacryloxypropyldimethyl methoxysilane and combinations thereof; and

[0183] 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (including MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methiacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate,4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, Ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate, hexahydrophthalate monohydroxyethyl(meth)acrylate,It comprises at least one zwitterion moiety selected from the group consisting of omega-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0184] Optionally, in embodiment (i), the zwitterionic copolymer is covalently bonded to the surface of the prepared substrate.

[0185] Optionally, in embodiment (i), the non-specific biomolecule adsorption and / or binding-resistant coating has reduced biomolecule binding compared to the untreated substrate.

[0186] Optionally, in embodiment (i), the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0187] Optionally, in embodiment (i), the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; and a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask.

[0188] Example of implementation (ii)

[0189] A method for providing a non-specific biomolecule adsorption and / or binding-resistant coated surface exhibiting low- or non-binding of biomolecules and / or low- or non-adsorption of biomolecules according to embodiment (ii),

[0190] (a) a step of providing a substrate to a reaction chamber;

[0191] (b) a step of forming a vacuum in the reaction chamber;

[0192] (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0193] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0194] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0195] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0196] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0197] (h) Optionally waiting step;

[0198] (i) A method comprising the steps of removing the copolymer, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface is described.

[0199] The method of implementation example (ii)

[0200] (a) SiOx - A step of providing a substrate which is a coated glass surface reaction chamber;

[0201] (b) a step of forming a vacuum in the reaction chamber;

[0202] (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0203] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0204] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0205] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0206] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0207] (h) Optionally waiting step;

[0208] (i) a step of removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the surface to thereby form a non-specific biomolecule adsorption and / or binding-resistant coated surface.

[0209] The method of Example (ii), wherein at least one silyl amine coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltriris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, Bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, Bis(triethoxysilylpropyl)amine,Bis(trimethoxysilylpropyl)amine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, Selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0210] The method of embodiment (ii), wherein at least one copolymerizable zwitterionic monomer comprises 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl phosphate 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,Hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0211] The method of embodiment (ii), wherein at least one copolymerizable epoxy monomer is glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, (oxiran-2-yl)methyl It is selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0212] The method of embodiment (ii), wherein the epoxy-modified zwitterionic copolymer is covalently bonded to the amine-modified substrate.

[0213] The method of Example (ii), wherein the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, methylene chloride, 1,2-dichloroethane and combinations thereof.

[0214] The method of embodiment (ii), wherein the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface has reduced biomolecule binding compared to an untreated substrate.

[0215] The method of embodiment (ii), wherein the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0216] The method of embodiment (ii), where the substrate is the surface of the container.

[0217] The method of embodiment (ii), wherein the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask.

[0218] The non-specific biomolecule adsorption and / or non-specific binding-resistant coated substrate of embodiment (ii) is,

[0219] (a) a step of providing a substrate to a reaction chamber;

[0220] (b) a step of forming a vacuum in the reaction chamber;

[0221] (c) a step of providing a gas containing O2 in the vicinity of the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0222] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0223] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0224] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0225] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0226] (h) Optionally waiting step;

[0227] (i) prepared by removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or binding-resistant coated surface, optionally heating the surface, thereby forming a non-specific biomolecule adsorption and / or binding-resistant coated substrate.

[0228] The method of embodiment (ii), wherein the substrate coated with non-specific biomolecule adsorption and / or non-specific binding resistance is

[0229] (a) SiO x - A step of providing a substrate which is a coated glass surface reaction chamber;

[0230] (b) a step of forming a vacuum in the reaction chamber;

[0231] (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0232] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0233] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0234] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0235] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0236] (h) Optionally waiting step;

[0237] (i) prepared by removing the copolymer solution, optionally drying the surface coated with non-specific biomolecule adsorption and / or non-specific binding resistance, optionally heating the surface, thereby forming a substrate coated with non-specific biomolecule adsorption and / or binding resistance.

[0238] The method of Example (ii), wherein at least one silyl amine coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltriris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, Bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, Bis(triethoxysilylpropyl)amine,Bis(trimethoxysilylpropyl)amine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, Selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0239] The method of embodiment (ii), wherein at least one copolymerizable zwitterionic monomer comprises 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl 2-(dimethylammonio)ethyl phosphate ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,Hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0240] The method of embodiment (ii), wherein at least one copolymerizable epoxy monomer is glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, (oxiran-2-yl)methyl It is selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0241] The method of embodiment (ii), wherein the non-specific biomolecule adsorption and / or binding-resistant coating has reduced biomolecule binding compared to an untreated substrate.

[0242] The method of embodiment (ii), wherein the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0243] The method of embodiment (ii), where the substrate is the surface of the container.

[0244] The method of embodiment (ii), wherein the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; and a 384-well plate.

[0245] The container of embodiment (ii) having an inner surface that is partially coated with a non-specific biomolecule adsorption and / or binding resistance coating is

[0246] (a) a step of providing a substrate to a reaction chamber;

[0247] (b) a step of forming a vacuum in the reaction chamber;

[0248] (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0249] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0250] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0251] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0252] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0253] (h) Optionally waiting step;

[0254] (i) prepared by removing the copolymer solution, optionally drying the surface coated with non-specific biomolecule adsorption and / or non-specific binding resistance, optionally heating the surface, thereby forming a container coated with non-specific biomolecule adsorption and / or binding resistance.

[0255] The container of embodiment (ii) having an inner surface that is partially coated with a non-specific biomolecule adsorption and / or binding resistance coating is

[0256] (a) SiO x - A step of providing a substrate which is a coated glass surface reaction chamber;

[0257] (b) a step of forming a vacuum in the reaction chamber;

[0258] (c) a step of providing a gas containing O2 near the substrate surface, optionally containing argon, and optionally containing nitrogen;

[0259] (d) a step of generating plasma from a gas, thereby forming a prepared substrate surface, and optionally heating the substrate;

[0260] (e) a step of providing an amine-modified substrate by providing a vapor comprising at least one silylamine coupling agent;

[0261] (f) optionally, a step of providing a copolymer solution comprising a solvent in the presence of a polymerization initiator, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer;

[0262] (g) a step of reacting the copolymer with an amine-modified substrate and optionally, heating the substrate;

[0263] (h) Optionally waiting step;

[0264] (i) prepared by removing the copolymer solution, optionally drying the surface coated with non-specific biomolecule adsorption and / or non-specific binding resistance, optionally heating the surface, thereby forming a container coated with non-specific biomolecule adsorption and / or binding resistance.

[0265] The vessel of embodiment (ii), wherein at least one silylamine coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltriris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)], aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, Bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, Bis(triethoxysilylpropyl)amine,Bis(trimethoxysilylpropyl)amine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, Selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof.

[0266] The vessel of embodiment (ii), wherein at least one copolymerizable zwitterionic monomer comprises 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl 2-(dimethylammonio)ethyl phosphate 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl ester); 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate,3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, 2-hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate; polyalkylene glycol(meth)acrylate monomers diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol(meth)acrylate, methoxypolyethylene glycol(meth)acrylate, methoxypolypropylene glycol(meth)acrylate; ω-carboxy(meth)acrylate, phthalate monohydroxyethyl(meth)acrylate,Hexahydrophthalic acid monohydroxyethyl (meth)acrylate, ω-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, (meth)acryloyloxyethyl succinate; selected from the group consisting of N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA), β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate and sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof.

[0267] The vessel of embodiment (ii), wherein at least one copolymerizable epoxy monomer is glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, (oxiran-2-yl)methyl It is selected from the group consisting of 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof.

[0268] The vessel of embodiment (ii), wherein the non-specific biomolecule adsorption and / or binding resistance coating has reduced biomolecule binding compared to the untreated substrate.

[0269] The vessel of embodiment (ii), wherein the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins.

[0270] The vessel of embodiment (ii), wherein the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette; a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; and a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask. means of solving the problem

[0271] In this specification, a method for reducing biomolecule attachment to a surface is disclosed. A method for treating a surface, optionally all or part of a substrate or a surface of a material, is provided, most generally comprising treating the surface with a conversion plasma of one or more non-polymerizable compounds to form a treated contact surface.

[0272] The terms "contact surface" and "surface" have the same meaning unless otherwise explicitly stated or specified by the context in which these terms are used; each of these terms refers to a surface located in contact with a sample or other material and possesses surface properties that determine its interaction with the sample and other material in contact. Some examples of contact surfaces are the inner surface of a container (e.g., the boundary of the container's lumen) or the outer surface of a container, sheet, block, or other object.

[0273] The term "internal portion" specifies a part of the bulk article or coating that is not the contact surface, but forms part of the interior of the bulk article or coating. In an embodiment where the contact surface of the substrate is treated to modify its properties, the internal portion of the substrate includes any portion that is not modified by the treatment.

[0274] The term “biomolecule” is used in connection with any embodiment to comprise any nucleotide or peptide, or any combination thereof. Nucleotides include oligonucleotides and polynucleotides, also known as nucleic acids, such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Peptides include amino acids, oligopeptides, polypeptides, and proteins. Nucleotides and peptides further comprise modified or derivatized nucleotides and peptides attached to surfaces not treated according to the present art.

[0275] The biomolecules defined herein include, but are not limited to, one or more of the following aqueous proteins: mammalian serum albumin, e.g. bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g. blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g. hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin, and pharmaceutical-grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, pro-peptide, or mature variant of these proteins; and combinations of two or more of these.

[0276] For any embodiment, biomolecule attachment to a surface is defined as a decrease in the aqueous concentration of biomolecules dispersed in an aqueous medium kept in contact with the surface. This is not limited to the mechanism of concentration reduction, whether it is literal "attachment," adsorption, or another mechanism.

[0277] "Plasma" as described in any embodiment has its conventional meaning in physics as one of the four fundamental states of matter, and is characterized by extensive ionization of its constituent particles, which are generally in gaseous form, and incandescent (i.e., producing a glow discharge meaning emitting light).

[0278] "Conversion plasma treatment" refers to any plasma treatment that reduces the attachment of one or more biomolecules to a treated contact surface.

[0279] "Conditioning plasma treatment" refers to any plasma treatment of a surface to prepare the surface for additional conversion plasma treatment. "Conditioning plasma treatment" includes, by itself, a plasma treatment that reduces the attachment of one or more biomolecules to the treated contact surface, but is followed by a conversion plasma treatment that further reduces the attachment of one or more biomolecules to the treated contact surface. Additionally, "conditioning plasma treatment" includes, by itself, a plasma treatment that does not reduce the attachment of one or more biomolecules to the treated contact surface.

[0280] "Remote" conversion plasma processing is, generally speaking, for example, cm 3It is a conversion plasma treatment of a surface located at a "remote" point, wherein the plasma radiant energy density, expressed in joules, is substantially lower than the maximum radiant energy density at any point of the plasma glow discharge (hereinafter referred to as the "brightest point"), but the remote surface is sufficiently close to a portion of the glow discharge to reduce the attachment of one or more biomolecules to the treated remote surface. "Remote" is defined in the same manner as with respect to remote conditioning plasma treatment, except that the remote surface must be sufficiently close to a portion of the glow discharge to condition the surface.

[0281] The radiant energy density at the brightest point of the plasma is determined spectrophotometrically by measuring the radiant intensity of the strongest emitted ray in the visible spectrum (wavelengths of 380 nanometers (nm) to 750 nm) at the brightest point. The radiant energy density at a remote point is determined spectrophotometrically by measuring the radiant energy density of the same emitted ray at the remote point. The "remoteness" of a point is quantified by measuring the ratio of the radiant energy density at the remote point to the radiant energy density at the brightest point. This specification quantitatively defines "remote" as a specific range of such a ratio. Broadly, the ratio is 0 to 0.5, optionally 0 to 0.25, optionally about 0, and optionally exactly 0. Remote conversion plasma treatment can be performed when the ratio is zero, even if it does not exhibit measurable visible light at a remote point, because the dark discharge region or afterglow region of the plasma contains energy species that do not have enough energy to emit light but have enough energy to modify the treated contact surface and reduce the attachment of one or more biomolecules.

[0282] "Non-polymerizable compounds" are defined as compounds that do not polymerize on a contact surface treated under conditions used for a specific plasma treatment of the surface for all operational embodiments, nor do they otherwise form an additional coating. A number of non-limiting examples of compounds that may be used under non-polymerizable conditions are as follows: O2, N2, air, O3, N2O, H2, H2O2, NH3, Ar, He, Ne, and any combination of two or more of the aforementioned. These may also include alcohols, organic acids, and polar organic solvents, as well as materials that may be polymerized under plasma conditions different from those used. "Non-polymerizable" includes compounds that react with and bind to an existing polymer surface and locally modify its composition on the surface. An essential feature of a non-polymerizable coating is that it does not increase in thickness (i.e., does not form an additional coating) as treatment time increases.

[0283] "Material" is an article or other solid form (e.g., granules, beads, or particles).

[0284] "Surface" is broadly defined as the original surface of the substrate (whereas "surface" is also used anywhere in this specification, it includes a portion of the surface), or a coated or treated contact surface prepared by any suitable coating or treatment method, such as liquid application, condensation from a gas, or plasma-enhanced chemical vapor deposition performed under conditions effective for forming a coating on the substrate.

[0285] For all embodiments, the treated contact surface is defined as a surface that is plasma treated as described herein and exhibits reduced adhesion by biomolecules as a result of such treatment.

[0286] The terms "optional" and "alternatively" are deemed to have the same meaning in this specification and claims and may be used interchangeably.

[0287] "Material" may be any material forming a substrate, including, but not limited to, a thermoplastic material in any embodiment, optionally a thermoplastic injection-moldable material. A substrate according to any embodiment may be made from materials including, but not limited to, the following, for example: olefin polymers; polypropylene (PP); polyethylene (PE); cyclic olefin copolymer (COC); cyclic olefin polymer (COP); polymethylpentene; polyester; polyethylene terephthalate; polyethylene naphthalate; polybutylene terephthalate (PBT); PVdC (polyvinylidene chloride); polyvinyl chloride (PVC); polycarbonate; polymethyl methacrylate; polylactic acid; polylactic acid; polystyrene; hydrogenated polystyrene; poly(cyclohexylethylene) (PCHE); epoxy resin; nylon; polyurethane polyacrylonitrile; polyacrylonitrile (PAN); ionomer resin; or Surlyn® ionomer resin.

[0288] The term “container” as used throughout this specification may be any type of article configured to contain or transport a liquid, gas, solid, or any two or more of these. An example of a container is an article having at least one opening (e.g., one, two, or more depending on the application) and a wall defining an internal contact surface.

[0289] The present method for treating a surface, optionally a surface of a substrate, comprises the step of treating the surface with a conversion plasma of one or more nonpolymer compounds in a chamber to form a treated contact surface.

[0290] A wide variety of different surfaces may be treated according to any embodiment. One example of a surface is the lumen surface of a container, where the container is, for example, a vial, bottle, jar, syringe, cartridge, blister package, or ampoule. Further examples, the surface of the material may be the fluid surface of a laboratory article, for example, a microplate, centrifuge tube, pipette tip, well plate, microwell plate, ELISA plate, microtiter plate, 96-well plate, 384-well plate, centrifuge tube, chromatography vial, vacuum blood collection tube, or specimen tube.

[0291] The treated contact surface of any embodiment is optionally PECVD-deposited SiO x C y H z or SiN x C y H z It may be a coating or layer of, where x is about 0.5 to about 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is about 0.6 to about 3 as measured by XPS, and z is about 2 to about 9 as measured by Rutherford backscatter spectroscopy (RBS). Another example of a surface to be treated is SiO₂. x (where x is about 1.5 to about 2.9 as measured by XPS), optionally a barrier coating or layer of an oxide or nitride of an organometallic precursor that is a compound of a metal element of Group III and / or Group IV of the periodic table, for example, Group III is boron, aluminum, gallium, indium, thallium, scandium, yttrium, or lanthanum (aluminum and boron preferred), and Group IV is silicon, germanium, tin, lead, titanium, zirconium, hafnium, or thorium (silicon and tin preferred).

[0292] In any embodiment, the gas or gases used to treat the surface may be an inert gas or a reactive gas and may be any of the following gases: O2, N2, air, O3, N2O, NO2, N2O4, H2, H2O2, H2O, NH3, Ar, He, Ne, Xe, Kr, nitrogen-containing gas, other non-polymerizable gas, Ar / O2 mixture, gas combination including an N2 / O2 mixture after a pretreatment conditioning step with Ar, volatile polar organic compounds, C1-C 12 Combination of hydrocarbon and oxygen; C1-C 12 A combination of hydrocarbons and nitrogen; silicon-containing gases; or a combination of two or more of these. The treatment utilizes non-polymerizable gases as defined herein.

[0293] Volatile polar organic compounds of any embodiment are, for example, water, for example, tap water, distilled water, or deionized water; alcohols, for example, C1-C 12 Alcohols, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, s-butanol, t-butanol; glycols, e.g., ethylene glycol, propylene glycol, butylene glycol, polyethylene glycol, and other glycols; glycerin, C1-C 12 Linear or cyclic ethers, e.g., dimethyl ether, diethyl ether, dipropyl ether, dibutyl ether, glyme (CH3OCH2CH2OCH3); chemical formulas such as diethylene oxide, triethylene oxide, and tetraethylene oxide -CH2CH2O n - Cyclic ethers; cyclic amines; cyclic esters (lactones), e.g., acetolactone, propiolactone, butyrolactone, valerolactone, and caprolactone; C1-C 12 Aldehydes, e.g., formaldehyde, acetaldehyde, propionaldehyde, or butyraldehyde; C1-C 12 Ketones, e.g., acetone, diethyl ketone, dipropyl ketone, or dibutyl ketone; C1-C 12Carboxylic acids, e.g., formic acid, acetic acid, propionic acid, or butyric acid; ammonia, C1-C 12 Amines, e.g., methylamine, dimethylamine, ethylamine, diethylamine, propylamine, butylamine, pentylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, or dodecylamine; hydrogen fluoride, hydrogen chloride, C1-C 12 Epoxide, for example, ethylene oxide or propylene oxide; or any combination of two or more of these.

[0294] C1-C of any implementation example 12 The hydrocarbon may optionally be methane, ethane, ethylene, acetylene, n-propane, i-propane, propene, propine; n-butane, i-butane, t-butane, butane, 1-butyne, 2-butyne, or any combination of two or more of these.

[0295] The silicon-containing gas of any embodiment may be a silane, an organosilicon precursor, or a combination of any two or more of these. The silicon-containing gas may be a non-cyclic or cyclic substituted or unsubstituted silane that optionally comprises, essentially comprises, or consists of any one or more of the following: substituted or unsubstituted Si1-Si4 silanes, e.g., silane, disilane, trisilane, or tetrasilane; hydrocarbon or halogen-substituted Si1-Si4 silanes, e.g., fluorinated silanes such as tetramethylsilane (TetraMS), tetraethylsilane, tetrapropylsilane, tetrabutylsilane, trimethylsilane (TriMS), triethylsilane, tripropylsilane, tributylsilane, trimethoxysilane, hexafluorodisilane, cyclic silanes such as octamethylcyclotetrasilane or tetramethylcyclotetrasilane, or a combination of any two or more of these. The silicon-containing gas may be a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or any combination of two or more of these, for example, hexamethyldisiloxane (HMDSO), tetramethyldisiloxane (TMDSO), octamethylcyclotetrasiloxane (OMCTS), tetramethyldisilazane, hexamethyldisilazane, octamethyltrisilazane, octamethylcyclotetrasilazane, tetramethylcyclotetrasilazane, or any combination of two or more of these.

[0296] In any embodiment, the output used to excite the plasma used for plasma treatment may be, for example, 1 to 1000 watts, optionally 100 to 900 watts, optionally 50 to 600 watts, optionally 100 to 500 watts, optionally 500 to 700 watts, optionally 1 to 100 watts, optionally 1 to 30 watts, optionally 1 to 10 watts, and optionally 1 to 5 watts.

[0297] In any embodiment, the frequency or type of energy of the electrical output used to excite the plasma used in plasma treatment may be any type of energy that ignites the plasma in the plasma zone. For example, this may be direct current (DC) or alternating current (electromagnetic energy) with a frequency of 3 Hz to 300 GHz. Electromagnetic energy in this range generally includes radio frequency (RF) energy and microwave energy, and more particularly characterized by extremely low frequency (ELF) of 3 to 30 Hz, super low frequency (SLF) of 30 to 300 Hz, voice frequency or very low frequency (VF or ULF) of 300 Hz to 3 kHz, very long frequency (VLF) of 3 to 30 kHz, low frequency (LF) of 30 to 300 kHz, medium frequency (MF) of 300 kHz to 3 MHz, high frequency (HF) of 3 to 30 MHz, very short frequency (VHF) of 30 to 300 MHz, very high frequency (UHF) of 300 MHz to 3 GHz, super high frequency (SHF) of 3 to 30 GHz, extremely high frequency (EHF) of 30 to 300 GHz, or any combination of two or more of these frequencies. For example, as two non-limiting examples of commonly used frequencies, high-frequency energy, typically 13.56 MHz, is useful RF energy, and ultra-high-frequency energy, typically 2.54 GHz, is useful microwave energy.

[0298] In any embodiment, the plasma excitation energy may be continuous during the processing step or may be pulsed several times during the processing step. When pulsed, it may be pulsed on for a time ranging from 1 millisecond to 1 second and then pulsed off for a time ranging from 1 millisecond to 1 second, alternating in a regular or variable order during the plasma processing. One full duty cycle (one "on" period + one "off" period) may have a length of 1 to 2000 milliseconds (ms), optionally 1 to 1000 milliseconds (ms), optionally 2 to 500 ms, optionally 5 to 100 ms, and optionally 10 to 100 ms.

[0299] Optionally, in any embodiment, the relationship between power on and power off in a duty cycle may be such that, for example, 1 to 90 percent of the time, optionally 1 to 80 percent of the time, optionally 1 to 70 percent of the time, optionally 1 to 60 percent of the time, optionally 1 to 50 percent of the time, optionally 1 to 45 percent of the time, optionally 1 to 40 percent of the time, optionally 1 to 35 percent of the time, optionally 1 to 30 percent of the time, optionally 1 to 25 percent of the time, optionally 1 to 20 percent of the time, optionally 1 to 15 percent of the time, optionally 1 to 10 percent of the time, and optionally 1 to 5 percent of the time, the power may be on for the remainder of each duty cycle.

[0300] Literature [Mark J. Kushner, PulsedPlasma- PulsedInjection Sources For Remote Plasma Activated Chemical Vapor Deposition Plasma pulsing described in [J. APPL. PHYS.73, 4098 (1993)] may be optionally used.

[0301] During plasma treatment according to any embodiment, the flow rate of the treatment gas may be 1 to 300 sccm (standard cubic centimeters per minute), optionally 1 to 200 sccm, optionally 1 to 100 sccm, optionally 1 to 50 sccm, optionally 5 to 50 sccm, and optionally 1 to 10 sccm.

[0302] Optionally, in any embodiment, the plasma chamber is depressurized to a base pressure of 0.001 millitor (mTorr, 0.00013 Pascals) to 100 Torr (13,000 Pascals) before supplying gas. Optionally, in any embodiment, the supply gas pressure may be in the range of 0.001 to 10,000 mTorr (0.00013 to 1300 Pascals), optionally 1 mTorr to 10 Torr (0.13 to 1300 Pascals), optionally 0.001 to 5000 mTorr (0.00013 to 670 Pascals), and optionally 1 to 1000 millitor (0.13 to 130 Pascals).

[0303] In any embodiment, the treatment volume in which the plasma is generated may be, for example, 100 mL to 50 liters, preferably 8 to 20 liters. Optionally, if the surface to be treated is the inner surface of a vessel having a lumen volume smaller than 100 mL, the treatment volume may be limited to less than such lumen volume. Accordingly, for example, a vessel having a lumen volume of 0.1 to 100 mL, or alternatively, 0.5 to 10 mL, is considered as the treatment volume.

[0304] In any embodiment, the plasma treatment time may be, for example, 1 second to 300 seconds, optionally 3 seconds to 300 seconds, optionally 30 seconds to 300 seconds, optionally 150 seconds to 250 seconds, optionally 150 seconds to 200 seconds, and optionally 90 seconds to 180 seconds.

[0305] The number of plasma treatment steps may vary in any embodiment. For example, one plasma treatment may be used; optionally, two or more plasma treatments may be used using the same or different conditions.

[0306] In any embodiment, the plasma processing device used may be any suitable device, for example, the device of FIG. 1, FIG. 7, FIG. 8, or FIG. 10 described herein as a few examples. For example, a plasma processing device of the type utilizing the lumen of a vessel to be processed as a vacuum chamber, as illustrated in FIG. 2 of U.S. Patent No. 7,985,188, may also be used in any embodiment.

[0307] The plasma treatment process of any embodiment may optionally be combined with a treatment using an ionizing gas. The ionizing gas may be any gas identified as suitable for plasma treatment, as some examples. The ionizing gas may be delivered in any suitable manner. For example, it may be delivered from an ionizing blow-off gun or other ionizing gas source. Convenient gas delivery pressures are 1 to 120 psi (pounds per square inch) (6 to 830 kPa, kilopascals) (gauge or, optionally, absolute pressure), optionally 50 psi (350 kPa). The moisture content of the ionizing gas may be 0 to 100%. The polarized contact surface treated with the ionizing gas may be performed for any suitable treatment time, for example, 1 second to 300 seconds, optionally 10 seconds.

[0309] Polymerizable substrate composition

[0310] Optionally, in any embodiment, the treatment result is a polymerizable substrate essentially comprising a contact surface and an internal portion. Optionally, in any embodiment, the contact surface comprises 1 to 30 atomic%, optionally 5 to 20 atomic%, optionally 5 to 10 atomic% oxygen atoms; 0 to 30 atomic%, optionally 0 to 20 atomic%, optionally 0 to 10 atomic% nitrogen atoms; and 80 to 99 atomic%, optionally 80 to 95 atomic%, optionally 90 to 95 atomic% carbon atoms, wherein the atomic% values ​​are measured by X-ray photoelectron spectroscopy (XPS).

[0311] Optionally, in any embodiment, oxygen and / or nitrogen atoms within the described proportions are grafted onto carbon atoms. Alternatively, carbon, oxygen, and nitrogen atoms may be deposited on a substrate to form a contact surface.

[0312] Optionally, in any embodiment, the internal portion of the substrate comprises at least 80 atomic%, optionally at least 85 atomic%, optionally at least 90 atomic%, optionally at least 95 atomic%, optionally 100 atomic% of carbon atoms, and atomic% of carbon atoms greater than that of the contact surface.

[0313] Optionally, in any embodiment, the contact surface comprises oxygen-grafted carbon atoms of 0.1 to 10 atomic%, optionally 0.1 to 5 atomic%, and optionally 1 to 5 atomic%.

[0314] Optionally, in any embodiment, the contact surface comprises 0.1 to 10 atomic percent, optionally 0.1 to 5 atomic percent, of hydrogen bond acceptor groups. Examples of such hydrogen bond acceptor groups are, without limitation, -N bonded to a carbon in each case. +It includes a moiety selected from -, -N-, =O, -O-, -O2, -O3, C=O, OC=O, COC, or ≡=N, optionally selected from these or any combination of two or more of these.

[0315] Optionally, in any embodiment, the contact surface, when measured by X-ray photoelectron spectroscopy (XPS), is a polar grafted species, optionally C=O (carbonyl), COC (ether), CNC (amine), CN + -C (ammonium), CO2 (carboxyl), CO3, Si=O, Si-O-Si, Si-N-Si, Si-N + It includes carbon or silicon compounds modified from one or more of -Si, SiO2, SiO3, C≡=N, Si≡=N, or combinations of two or more of these.

[0316] Optionally, in any embodiment, the contact surface comprises a thermoplastic material, e.g., a thermoplastic resin, e.g., an injection-molded thermoplastic resin. Some non-limiting examples of suitable resins include hydrocarbon polymers, e.g., olefin polymers, polypropylene (PP), polyethylene (PE), cyclic olefin copolymers (COC), cyclic olefin polymers (COP), polymethylpentene, polystyrene, hydrogenated polystyrene, polycyclohexylethylene (PCHE), or combinations of two or more of these, or heteroatom-substituted hydrocarbon polymers, e.g., polyester, polyethylene terephthalate, polyethylene naphthalate, polybutylene terephthalate (PBT), polyvinylidene chloride (PVdC), polyvinyl chloride (PVC), polycarbonate, polylactic acid, epoxy resin, nylon, polyurethane polyacrylonitrile, polyacrylonitrile (PAN), ionomer resin, Surlyn® ionomer resin, or any combination, composite, or blend of any two or more of the above materials.

[0317] Optionally, in any embodiment, the contact surface has a biomolecule recovery percentage of at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 45%, optionally at least 50%, optionally at least 55%, optionally at least 60%, optionally at least 65%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, optionally at least 90%, optionally at least 95%. Optionally, in any embodiment, the biomolecule recovery percentage is mammalian serum albumin; bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN); egg white ovotransferrin (conalbumin); membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin; pharmaceutical protein; blood or blood component protein; and any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins; and at least one of a combination of two or more of these is determined.

[0318] Optionally, in any embodiment, for a BSA with an atomic mass of 66,000 daltons, the percentage of biomolecule recovered is at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, optionally at least 90%, optionally at least 95%, optionally at least 99%, optionally 10% to 90%, optionally 20% to 90%, optionally 30% to 90%, optionally 40% to 90%, optionally 50% to 90%, optionally 60% to 90%, optionally 70% to 90%, optionally 80% to 90%.

[0319] Optionally, in any embodiment, in the case of an FBG with an atomic mass of 340,000 daltons, the percentage of biomolecule recovered is at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, optionally at least 90%, optionally at least 95%, optionally at least 99%, optionally 10% to 90%, optionally 20% to 90%, optionally 30% to 90%, optionally 40% to 90%, optionally 50% to 90%, optionally 60% to 90%, optionally 70% to 90%, optionally 80% to 90%, optionally 15% to 20%.

[0320] Optionally, in any embodiment, when the TFN has an atomic mass of 80,000 daltons, the percentage of biomolecule recovered is at least 30%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, optionally at least 90%, optionally at least 95%, optionally at least 99%, optionally 10% to 90%, optionally 20% to 90%, optionally 30% to 90%, optionally 40% to 90%, optionally 50% to 90%, optionally 60% to 90%, optionally 70% to 90%, optionally 80% to 90%, optionally 30% to 50%.

[0321] Optionally, in any embodiment, when the PrA has an atomic mass of 45,000 daltons, the percentage of biomolecule recovered is at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, optionally at least 90%, optionally at least 95%, optionally at least 99%, optionally 10% to 90%, optionally 20% to 90%, optionally 30% to 90%, optionally 40% to 90%, optionally 50% to 90%, optionally 60% to 90%, optionally 70% to 90%, optionally 80% to 90%, optionally 10% to 90%.

[0322] Optionally, in any embodiment, when the PrG has an atomic mass of 20,000 daltons, the percentage of biomolecule recovered is at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, optionally at least 90%, optionally at least 95%, optionally at least 99%, optionally 10% to 90%, optionally 20% to 90%, optionally 30% to 90%, optionally 40% to 90%, optionally 50% to 90%, optionally 60% to 90%, optionally 70% to 90%, optionally 80% to 90%, optionally 5% to 90%.

[0323] Optionally, in any embodiment, the contact surface is a lumen surface of a container, e.g., a fluid contact surface of a laboratory article. Examples of suitable articles of laboratory articles include microplates, centrifuge tubes, pipette tips, well plates, microwell plates, ELISA plates, microtiter plates, 96-well plates, 384-well plates, vials, bottles, bottles, syringes, cartridges, blister packages, ampoules, vacuum blood collection tubes, specimen tubes, centrifuge tubes, or chromatography vials.

[0324] Optionally, in any embodiment, the contact surface is in contact with an aqueous protein.

[0325] Optionally, in any embodiment, the contact surface has a contact angle with distilled water of 0° to 90°, optionally 20° to 80°, optionally 40° to 80°, optionally 50° to 70°, and optionally 55° to 65°.

[0326] Optionally, in any embodiment, the contact surface has an electrostatic charge accumulation of the converted and optionally conditioned contact surface of less than 5 kilovolts (5 kV / cm) per 1 cm, optionally less than 3 kV / cm, optionally less than 2 kV / cm, and optionally less than 1 kV / cm.

[0327] Optionally, in any embodiment, the contact surface is treated with a conditioning plasma, a conversion plasma, or both of one or more non-polymerizable compounds to form a surface. Optionally, in any embodiment, the non-polymerizable compound comprises, essentially comprises, or consists of one or more members selected from the group consisting of O2, N2, air, O3, N2O, H2, H2O, H2O2, NH3, Ar, He, and Ne.

[0328] Optionally, in any embodiment, the contact surface is a PECVD deposition coating with a thickness of 5 to 1000 nm. Optionally, in any embodiment, the PECVD deposition coating is applied using any one or combination of a gas precursor comprising siloxane, organosiloxane, or polyethylene glycol (PEG); or a monomer gas precursor comprising acetylene, methane, propane, butane, or ethane; and / or a comonomer gas comprising air, oxygen, or water vapor. Optionally, in any embodiment, the PECVD deposition coating is an amorphous carbon coating further comprising oxygen and optionally nitrogen heteroatoms. For example, the amorphous carbon coating may be applied using a reactive gas comprising a carbon-containing monomer gas precursor, e.g., acetylene, ethylenemethane, ethane, propane, butane, or a combination of two or more of these, and air, oxygen, water vapor, or a combination of two or more of these.

[0330] Biomolecular Contact and Recovery

[0331] After plasma treatment(s) of any embodiment, the treated contact surface, e.g., the surface of the vessel lumen, may come into contact with an aqueous protein or other biomolecule. Some non-limiting examples of suitable proteins are aqueous proteins comprising: mammalian serum albumin, e.g. bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g. blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g. hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin, and pharmaceutical-grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins; and a combination of two or more of these.

[0332] Optionally, the treated contact surface has a protein recovery percentage higher than the protein recovery percentage of the unconditioned and unconverted surface, for at least one of bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g., blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g., hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin and pharmaceutical grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of such proteins or peptides.

[0334] A more detailed first embodiment

[0335] A container having a substrate according to a more detailed first embodiment may be manufactured, for example, from any of the materials defined above. For applications where a transparent glass-like polymer is desired (e.g., syringes and vials), cyclic olefin polymers (COP), cyclic olefin copolymers (COC), polymethyl methacrylate, polyethylene terephthalate, or polycarbonate may be preferred. Linear polyolefins, for example, polypropylene, and aromatic polyolefins, for example, polystyrene, are also considered. Such substrates may be produced with very tight and precise tolerances (much tighter than generally achievable with glass) by, for example, injection molding or injection stretch blow molding (which is also classified as injection molding in any embodiment of this specification). Plasma-treated glass substrates, for example, borosilicate glass substrates, are also considered.

[0336] A vessel according to a more detailed first embodiment may be a vessel, for example, a sample tube or cuvette for collecting or storing a biological fluid, for example, blood or urine, for holding a fluid, for example, a biological material or a biologically active compound or composition; a syringe (or part thereof, for example, a syringe barrel) for storing or delivering a biologically active compound or composition, for example, a pharmaceutical or pharmaceutical composition; a vial for storing a biological material or a biologically active compound or composition; or a pipe or other conduit, for example, a catheter, for transporting a biological material or a biologically active compound or composition. Other non-limiting examples of the vessel considered include well or non-well slides or plates, for example, titer plates or micro-potency plates (also known as microplates). Other examples of the vessel include measuring and delivery devices such as pipettes, pipette tips, Erlenmeyer flasks, beakers, and graduated cylinders. The specific vessels described herein in relation to the actual reduction for the execution of non-limiting embodiments are polypropylene 96-well microplates and beakers. However, those skilled in the art will understand that the methods and equipment setups described herein may be modified and adapted according to the art to accommodate and process any type of surface or vessel or other type of object.

[0337] The surface of the container of the first embodiment in more detail may be made of the substrate material itself, for example, any thermoplastic resin listed above. Optionally, the substrate may be a bulk material or PECVD-deposited SiO₂. x C y H z or SiN x C y H zIt may be a pH protective coating or layer, where x is about 0.5 to about 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is about 0.6 to about 3 as measured by XPS, and z is about 2 to about 9 as measured by Rutherford backscatter spectroscopy (RBS). Another example of the substrate is PECVD-deposited SiO. x A barrier coating or layer of an oxide or nitride of an organometallic precursor that is a compound of a metal element of Group III and / or Group IV of the periodic table (wherein x is about 1.5 to about 2.9 as measured by XPS), optionally, a metal element of Group III and / or Group IV, for example, Group III is boron, aluminum, gallium, indium, thallium, scandium, yttrium, or lanthanum (aluminum and boron preferred), and Group IV is silicon, germanium, tin, lead, titanium, zirconium, hafnium, or thorium (silicon and tin preferred). Methods and equipment for depositing such a coating or layer are described in detail in WO2013 / 071138 published May 16, 2013, the whole of which is incorporated herein by reference.

[0338] The method according to the first embodiment, which is more detailed, utilizes remote conversion plasma treatment. Unlike direct plasma treatment, in the case of remote conversion plasma, a substantial amount of plasma ions or electrons do not come into contact with the surface of the article. Typically, lower-energy neutral species are present in the plasma afterglow, which has sufficient energy to react with the surface of the article without sputtering or other higher-energy chemical reactions induced by ions and electrons. The result of remote conversion plasma is weak surface modification without the high-energy effects of "direct" plasma.

[0339] The method according to a more detailed first embodiment utilizes non-polymerizable gases such as O2, N2, air, O3, N2O, H2, H2O2, NH3, Ar, He, and Ne, other non-polymerizable gases, and any combination of two or more of the aforementioned. These methods may also include non-polymerizable alcohols, non-polymerizable organic acids, and non-polymerizable polar organic solvents. Experiments were conducted in which a conditioning step (non-polymerizable compound step) was performed using a pretreatment conditioning step with Ar, N2, an Ar / O2 mixture, or an N2 / O2 mixture and Ar. These non-polymerizable gases and other non-polymerizable gases do not necessarily deposit a coating. Rather, they react with the surface to modify the surface, such as by forming a treated contact surface, wherein the percentage of biomolecule recovery on the treated contact surface is higher than the percentage of biomolecule recovery on a surface that is not conditioned and is not converted. For example, surface reactions can generate new chemical functional groups on the surface, including but not limited to carbonyl, carboxyl, hydroxyl, nitrile, amide, and amine groups. These polar chemical groups are considered to increase the surface energy and hydrophilicity of hydrophobic polymers that, in the absence of these groups, unconditioned and unconverted surfaces may typically contain. While hydrophobic surfaces are generally good binding surfaces for biomolecules, hydrophilic surfaces that attract water molecules facilitate the blocking of biomolecule binding to such surfaces. Although the present invention is not limited to this theory of operation, this mechanism is considered to prevent biomolecule binding to the surface.

[0340] Optionally, the method according to the more detailed first embodiment may be used to reduce the tendency of a substrate surface to allow biomolecules to attach to the substrate surface. Preferably, the present method will reduce biomolecule attachment over a broad spectrum of biomolecules comprising, but not limited to, one or more of the following aqueous proteins: mammalian serum albumin, e.g. bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g. blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g. hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin, and pharmaceutical-grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, pro-peptide, or mature variant of these proteins; and a combination of two or more of these.

[0341] FIG. 1 is a schematic diagram of a remote conversion plasma processing apparatus of a more detailed first embodiment having common features with each of the more specific embodiments of FIG. 2, FIG. 6, FIG. 7, and FIG. 8 for performing remote conversion plasma processing in the present specification. Plasma gas (plasma is defined in the present specification as a visible glow discharge) from a fluid source (12) capable of supporting the generation of plasma in a plasma zone (15) having a boundary (20) is introduced into the plasma zone (15) through a fluid inlet (13), and plasma energy from a plasma energy source (18) is provided to the plasma zone (15) to generate plasma having a boundary (20) in the plasma zone (15).

[0342] The plasma energy of the first embodiment in more detail can be any type of energy that ignites the plasma in the plasma zone (15). For example, it can be direct current (DC) or alternating current (electromagnetic energy) with a frequency of 3 Hz to 300 GHz. Electromagnetic energy in this range generally includes radio frequency (RF) energy and microwave energy, and more particularly characterized by extremely low frequency (ELF) of 3 to 30 Hz, super low frequency (SLF) of 30 to 300 Hz, voice frequency or very low frequency (VF or ULF) of 300 Hz to 3 kHz, very long frequency (VLF) of 3 to 30 kHz, low frequency (LF) of 30 to 300 kHz, medium frequency (MF) of 300 kHz to 3 MHz, high frequency (HF) of 3 to 30 MHz, very short frequency (VHF) of 30 to 300 MHz, very high frequency (UHF) of 300 to 3 GHz, super high frequency (SHF) of 3 to 30 GHz, extremely high frequency (EHF) of 30 to 300 GHz, or any combination of two or more of these frequencies. For example, as two non-limiting examples of commonly used frequencies, high-frequency energy, typically 13.56 MHz, is useful RF energy, and ultra-high-frequency energy, typically 2.54 GHz, is useful microwave energy.

[0343] The properties of the optimal applicator (23) of the first embodiment in more detail are determined by the frequency and output level of the energy, as is well known. When the plasma is excited by radio waves, for example, the applicator (23) may be an electrode, whereas when the plasma is excited by microwave energy, for example, the applicator (23) may be a waveguide.

[0344] The afterglow region (24) of the first embodiment in more detail is located outside but close to the plasma boundary (20) and contains the processing gas (17). The afterglow region (24) may be the entire processing volume (10) located outside the plasma boundary (20) and within the reaction chamber wall (1) and cover (19), or the afterglow region (24) may be a subset of the processing volume (10) depending on the dimensions and conditions maintained within the processing volume. The processing gas (17) within the afterglow region (24) is not sufficiently ionized to form a plasma, but has sufficient energy to better modify the surface in contact with it than the same gas composition at the same temperature and pressure in the absence of plasma.

[0345] Those skilled in the art will understand that some gas compositions are chemically reactive enough to modify the substrate in the apparatus (9) of the more detailed first embodiment in the absence of plasma. The test regarding whether the area of ​​the remote conversion plasma processing apparatus, or an adjacent area, is within the afterglow with respect to the given equipment, plasma, gas supply, and pressure or vacuum conditions that produce a visible glow discharge outside the area is whether the substrate located within the area under the given equipment, plasma, gas supply, and pressure is modified compared to the substrate exposed to the same equipment, gas supply, and pressure or vacuum conditions when the plasma is not present in the area that generally defines the plasma zone as a result of the absence or insufficiency of the plasma energy (18) of the more detailed first embodiment.

[0346] The remote conversion plasma treatment of the first embodiment in more detail is performed by providing plasma to the plasma zone (15) to generate afterglow or remote conversion plasma (both terms refer to the same area) (24) within the afterglow zone, and by bringing the plasma into contact with a substrate surface that is at least partially disposed in the afterglow zone (24) to modify it.

[0347] As an option of a more detailed first embodiment of a remote conversion plasma processing device, a plasma gas enters a plasma zone, is excited to form a plasma, and then continues downstream to a afterglow zone (24) where it has less energy, defined as a processing gas (17), and comes into contact with a substrate. In other words, at least a portion of the gas flows through the plasma zone (15), is supplied with energy to form a plasma, and continues to the afterglow zone (24), where it has more energy in the plasma zone (15) and less energy when it enters the afterglow zone (24) (however, it still has energy compared to the gas before entering the plasma zone (15)). When this option is adopted, the plasma and the afterglow zone (24) are gas-connected, and at least a portion of the same gas is supplied through both zones. Optionally, if plasma is not generated in the entire cross-section of the flowing gas, some of the gas remains outside the boundary (20) of the plasma zone (15) to bypass the plasma and still flow through the afterglow zone (24), while the remaining gas flows through both the plasma zone (15) and the afterglow zone (24).

[0348] As another option in the remote conversion plasma processing device of the first embodiment in more detail, the plasma gas may be a different molecule from the processing gas (17) (nevertheless, the plasma gas and the processing gas may have the same composition or a different composition), and the plasma gas remains in the plasma zone (15) rather than the afterglow region (24) or is supplied only through the plasma zone (15), while the processing gas is energized by the plasma gas but is separate from the plasma gas and is not supplied with enough energy to form plasma in the afterglow region (24).

[0349] The properties of the applicator (23) of the first embodiment in more detail may vary depending on the application conditions, for example, the output level and frequency of the plasma energy (18). For example, the applicator may be composed of an electrode, an antenna, or a waveguide.

[0350] Optionally, the shielding portion (16) is positioned between the plasma and at least a portion of the substrate (14) in the processing area of ​​the more detailed first embodiment to prevent the plasma from coming into contact with the substrate (14), undesirably approaching the substrate (14), or having an uneven effect on the substrate (14). For example, in FIG. 1, the optional shielding portion (16) is perforated to enable gas flow through it, particularly the flow of neutral species that form afterglow, but the shielding portion (16) is configured or provided to prevent the plasma from penetrating the shielding portion of the more detailed first embodiment, suitably with respect to the selection of plasma-forming energy. For example, the size of the perforation may be determined so that the plasma-forming energy or plasma cannot pass through the shielding portion, or the shielding portion may be electrically deflected or grounded. This arrangement has the advantage that, where the plasma zone has a substantial area intersecting the shielding section, the substantial area is optionally flattened so that the plasma boundary (20) has a "flat spot" (26), as illustrated in FIG. 1 of a more detailed first embodiment, and that this flat spot can be positioned parallel to the surface of the substrate to be processed so that the plasma has the advantage of being equidistant over the substantial area, instead of ending in a tapered tail that extends much closer to one part of the substrate (14) than other parts of the substrate (14) that are not aligned with the tail, as illustrated in FIG. 8 of a more detailed first embodiment.

[0351] Another shielding option of the first embodiment in more detail is that the shielding is designed so as not to allow gas or plasma to pass through, and can act as an obstacle to the direct path between part or all of the plasma and part or all of the processing area. The obstacle can fill less than the entire cross-section of the gas flowing from the plasma area (15) to the afterglow area (24), so that the non-ionized gas can flow around the shielding and reach the afterglow area (24) by a bypass path, while the plasma cannot bypass or pass through it.

[0352] Another shielding option of the first embodiment in more detail is to position the substrate (14) to be processed during processing within the device such that a part of the substrate (14) capable of withstanding contact with plasma is exposed to the plasma, thereby shielding another part of the substrate (14) from the plasma or allowing another substrate to receive remote conversion plasma processing.

[0353] Another shielding option of the first embodiment in more detail is that the gas flow path through the plasma and the processing area is sharply bent, such as turning a 90-degree corner between the plasma and the processing area, so that the wall of the device itself can shield the processing area from the line of sight to the plasma under specific processing conditions.

[0354] The orientation of the substrate within the processing volume of the more detailed first embodiment may vary, and the substrate, applicator, gas, and vacuum source may be optionally arranged to provide substantially uniform or non-uniform exposure to the remote conversion plasma across the substrate.

[0355] Another option of the first embodiment in more detail is that the substrate itself acts as a reactor wall or part of a reactor wall, so that the treatment gas (17) introduced into the reactor can treat the part of the substrate acting as a reactor wall.

[0356] Another option in the first embodiment, which is more detailed, is to introduce a second non-polymerizable gas into the reactor that functions as a diluent gas in addition to the non-polymerizable compound or water vapor that is an activator of the treatment gas (17). The diluent gas is defined as a gas introduced into the fluid inlet (13) that does not substantially interact with the substrate (14) to the extent that it enters the treatment gas (17), considering the treatment apparatus and the applied conditions. The diluent gas may or may not participate in the formation of plasma. The diluent gas may be introduced through the inlet (13) or elsewhere in the reactor. The diluent gas may be added in a ratio of 1 volume% to 10,000 volume%, optionally 10 volume% to 1,000 volume%, optionally 100 volume% to 1,000 volume% of the addition ratio of the non-polymerizable compound or water vapor.

[0357] As another option in a more detailed first embodiment, some or all of the non-polymerizable compound or water vapor may be added to the treatment volume (10) in such a way that it bypasses the plasma zone (15) on its way to the treatment gas (17).

[0358] FIG. 2 of a more detailed first embodiment illustrates another embodiment of the apparatus of FIG. 1. This apparatus can again be used to perform remote conversion plasma processing according to the more detailed first embodiment. The chamber of this embodiment comprises a processing volume (10) defined and enclosed by reaction chamber walls (11), which are optionally non-electrically conductive. The processing volume (10) is provided with a fluid source (12) (in this case, a tubular fluid inlet (13) protruding axially into the processing volume (10), but other fluid sources, e.g., a "shower head" type fluid source, are considered). Optionally, the processing volume (10) may be defined by the processing chamber walls (11) or by a lumen within a vessel or other article to be processed. A supply gas is supplied into the processing volume (10). The plasma reaction chamber includes, as an optional feature, a vacuum source (22) for at least partially reducing the processing volume (10) relative to ambient pressure for use when plasma processing at reduced pressure, but plasma processing under suitable conditions at ambient atmospheric pressure or higher than ambient atmospheric pressure is also considered.

[0359] The plasma reaction chamber further includes an optional external applicator (23), which in this case is in the form of an electrode surrounding at least a portion of the plasma reaction chamber. A radio frequency (RF) plasma energy source (18) is coupled to the reaction chamber by the applicator (23) to provide an output that excites a gas to form a plasma. The plasma forms a visible glow discharge (20) that is optionally limited to a location very close to a fluid source (12).

[0360] Optionally, the microplate (14) may be oriented such that the surface of the microplate (14) to be treated (the surface configured and intended to contact and / or retain the biomolecule-containing solution) faces the fluid source (12). However, the surface to be treated may also face the opposite side of the fluid source (12) as illustrated in FIG. 2, or instead. Additionally, in the illustrated embodiment, the microplate (14) is shielded by a shielding member (16) so that the microplate (14) is not in the direct "line of sight" of the fluid source (12) (i.e., has an unobstructed path to the fluid source (12). As a non-limiting example, each surface of the microplate (14) may be located at a horizontal distance of approximately 2.75 inches (7 cm) from the fluid source, but operation is considered to be placed at a horizontal distance of 1 / 2 to 10 inches (1 to 25 cm), optionally 2.5 to 5.5 inches (6 to 14 cm), from the fluid source. In this way, the process relies on a remote conversion plasma (not a direct plasma) to process the surface of the microplate (14). In this non-limiting example, the system has a capacity of 20 parts (microplates) per batch with a total process time of 8 minutes per batch.

[0361] FIG. 6 of a more detailed first embodiment illustrates another embodiment of the apparatus of FIG. 1. In FIG. 6, the process used to process the microplate utilizes a radio-frequency (RF) plasma system. The system has a gas delivery input, a vacuum pump, and an RF power supply with a matching network. The microplate is illustrated as having its front surface containing the well (32) facing away from the plasma and is oriented to be shielded from the plasma along the perimeter of the chamber.

[0362] These details are illustrated in FIG. 6 of a more detailed first embodiment, which also illustrates another exemplary setup having all the elements of the apparatus of FIG. 2 of a more detailed first embodiment for use in a plasma reaction chamber for performing remote conversion plasma processing according to the more detailed first embodiment. The chamber of the more detailed first embodiment included a processing volume (10) defined and enclosed by a reaction chamber wall (11) having a fluid source (12) (in this case, a tubular fluid inlet (13) protruding axially into the processing volume (10), but other fluid sources, e.g., a "shower head" type fluid source, are considered). In this embodiment, the reaction chamber wall (11) was provided with a removable cover (13) that can be opened to allow a substrate to be inserted or removed, and can be sealed to accommodate the process and optionally depressurize the processing volume. In the more detailed first embodiment, the fluid source (12) was made of a metallic material, was electrically grounded, and also functioned as an applicator in the form of an internal electrode. As is well known, the plasma of the more detailed first embodiment can optionally be generated without an internal electrode.

[0363] The supply gas was supplied into the processing volume (10). The plasma reaction chamber included optional features of a vacuum source (22) for depressurizing the processing volume (10) at least partially. The plasma reaction chamber wall (11) also functioned as an external applicator or an electrode-shaped applicator (23) surrounding at least a portion of the plasma reaction chamber. In this case, a plasma energy source (18), which is a radio frequency (RF) source, was coupled to the applicator (23) defined by the reaction chamber wall (24) and the fluid source (12) to provide an output that excited the gas to form a plasma. The plasma zone (15) formed a visible glow discharge, which was limited to a location very close to the fluid source (12) by the plasma boundary (20). The afterglow region, also known as the remote conversion plasma region (24), is a radial or axial region outside the boundary (20) of the visible glow discharge, extending past the processed substrate.

[0364] A microplate (14) having a front side (28) and a back side (30) was oriented such that a well (32) on the front side of the microplate (14) to be processed (the front side configured and intended to contact / hold the biomolecule-containing solution) faced away from the fluid source (12) and the back side (30) faced toward the fluid source (12). The front side (28) of the microplate (14) was shielded by its own back side (30), blocking the front side (28) of the microplate from being in the direct “line of sight” of the fluid source (12). In this way, the process relied on a remote conversion plasma (not a direct plasma) to process the surface of the well (32).

[0365] FIG. 7 of a more detailed first embodiment illustrates another embodiment of the apparatus of FIG. 1 having corresponding features. The embodiment of FIG. 7 provides a plate electrode as an applicator and a "shower head" fluid inlet (13), which provides more uniform generation and application of the processing gas (17) over a wider area of ​​the substrate (14).

[0366] FIG. 8 of a more detailed first embodiment illustrates another embodiment of the device of FIG. 1 having corresponding features. The embodiment of FIG. 8 provides microwave plasma energy (18) delivered through an applicator (23) composed of a waveguide. In this embodiment, the plasma zone (15) and the substrate support (21) are provided in separate vessels connected by a conduit.

[0367] In a first embodiment optionally more detailed, the treated contact surface has a biomolecule recovery percentage higher than the biomolecule recovery percentage of an unconditioned and unconverted surface, for at least one of bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g., blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g., hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin and pharmaceutical grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins and combinations of two or more of these.

[0368] In one optional embodiment of the first embodiment more detailed, the plasma treatment process comprises, essentially comprises, or consists of the following two steps using a remote conversion plasma: (1) an oxygen plasma step (or more generally, a non-polymerizable compound plasma step) followed by (2) a water vapor plasma step. It should be understood that additional steps may be added prior to, between, or after the aforementioned steps, and that such additional steps may fall within the scope of the first embodiment more detailed. Additionally, it should be understood that the oxygen plasma step may utilize an optional gas for oxygen, including but not limited to nitrogen or any non-polymerizable gas listed herein. As another optional embodiment of the first embodiment more detailed, the plasma treatment process comprises, essentially comprises, or consists of using a remote conversion plasma of oxygen and water vapor combined in a single plasma step. This optional embodiment is characterized herein as a conversion step without a pre-conditioning step.

[0369] Optional process parameters for the conditioning step (non-polymerizable compound plasma step) and the second treatment step (water vapor plasma step) of the more detailed first embodiment are presented in Table 1 of the more detailed first embodiment.

[0370]

[0371] Optionally, the pretreatment step is not required prior to the non-polymerizable gas plasma step.

[0372] Optionally, in a more detailed first embodiment, the remote conversion plasma used to process the substrate surface may be an RF-generated plasma. Optionally, plasma-enhanced chemical vapor deposition (PECVD) or other plasma processes may be used according to a more detailed first embodiment.

[0373] Optionally, the processing volume in the plasma reaction chamber may be 100 mL to 50 liters, preferably 8 to 20 liters, for a specific application. Optionally, the processing volume may be generally cylindrical, but other shapes and configurations are also considered.

[0375] Processed entry disclosure

[0376] A treated substrate obtained by this method and other methods, and in particular, a treated contact surface are considered.

[0377] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface, when measured by X-ray photoelectron spectroscopy (XPS), comprises 1 to 30 atomic% grafted oxygen, optionally 2 to 20 atomic% grafted oxygen, optionally 4 to 12 atomic% grafted oxygen, optionally 1 to 2 atomic% grafted oxygen, optionally 2 to 3 atomic% grafted oxygen, optionally 3 to 4 atomic% grafted oxygen, optionally 4 to 5 atomic% grafted oxygen, optionally 5 to 6 atomic% grafted oxygen, optionally 6 to 7 atomic% grafted oxygen, optionally 7 to 8 atomic% grafted oxygen, optionally 8 to 9 atomic% grafted oxygen, optionally 9 to 10 atomic% grafted oxygen, and optionally 10 to 11 atomic% Grafted oxygen, optionally 11 to 12 atomic% grafted oxygen, optionally 12 to 13 atomic% grafted oxygen, optionally 13 to 14 atomic% grafted oxygen, optionally 14 to 15 atomic% grafted oxygen, optionally 15 to 16 atomic% grafted oxygen, optionally 16 to 17 atomic% grafted oxygen, optionally 17 to 18 atomic% grafted oxygen, optionally 18 to 19 atomic% grafted oxygen, optionally 19 to 20 atomic% grafted oxygen, optionally 20 to 21 atomic% grafted oxygen, optionally 21 to 22 atomic% grafted oxygen, optionally 22 to 23 atomic% grafted oxygen, optionally 23 to 24 atomic% grafted oxygen, optionally 24 1 to 25 atomic% grafted oxygen, optionally 25 to 26 atomic% grafted oxygen, optionally 26 to 27 atomic% grafted oxygen, optionally 27 to 28 atomic% grafted oxygen, optionally 28 to 29 atomic% grafted oxygen,Optionally comprises a carbon or silicon compound containing 29 to 30 atomic percent grafted oxygen.

[0378] The “atomic %” or “at. %” of a specific species, typically a chemical element, on a converted and selectively conditioned contact surface will be understood as dividing the number of atoms, molecules, or moietyes of that specific species detected by XPS by the number of all atoms, molecules, or moietyes of all species detected by XPS and multiplying by 100%. Accordingly, where 89 carbon atoms, 5 nitrogen atoms, and 11 oxygen atoms are all atoms detected on the substrate, the atomic % of carbon is as follows:

[0379] 100% Х 89 / (89 + 5 + 11) = 84.8 at.% C

[0380] As used herein, “grafted oxygen” or other grafted species refers to oxygen or other grafted species chemically (more specifically, covalently) bonded to atoms or atoms on the substrate surface when detected by XPS analysis. The species grafted onto the molecules of the polymer on the substrate surface are typically grafted between the ends of the polymer molecules, which are inserted into the polymer backbone or attached as pendant groups.

[0381] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface, when measured by X-ray photoelectron spectroscopy (XPS), is 0 to 30, optionally 0.1 to 30 atomic% grafted nitrogen, optionally 0.1 to 20 atomic% grafted nitrogen, optionally 0.1 to 10 atomic% grafted nitrogen, optionally 0.1 to 1 atomic% grafted nitrogen, optionally 1 to 2 atomic% grafted nitrogen, optionally 2 to 3 atomic% grafted nitrogen, optionally 3 to 4 atomic% grafted nitrogen, optionally 4 to 5 atomic% grafted nitrogen, optionally 5 to 6 atomic% grafted nitrogen, optionally 6 to 7 atomic% grafted nitrogen, optionally 7 to 8 atomic% grafted nitrogen, optionally 8 to 9 atomic% grafted nitrogen, optionally 9 to 10 atomic% grafted nitrogen, optionally 10 to 11 atomic% grafted nitrogen, optionally 11 to 12 atomic% grafted nitrogen, optionally 12 to 13 atomic% grafted nitrogen, optionally 13 to 14 atomic% grafted nitrogen, optionally 14 to 15 atomic% Grafted nitrogen, optionally 15 to 16 atomic% grafted nitrogen, optionally 16 to 17 atomic% grafted nitrogen, optionally 17 to 18 atomic% grafted nitrogen, optionally 18 to 19 atomic% grafted nitrogen, optionally 19 to 20 atomic% grafted nitrogen, optionally 20 to 21 atomic% grafted nitrogen, optionally 21 to 22 atomic% grafted nitrogen, optionally 22 to 23 atomic% grafted nitrogen, optionally 23 to 24 atomic% grafted nitrogen, optionally 24 to 25 atomic% grafted nitrogen, optionally 25 to 26 atomic% grafted nitrogen, optionally 26 to 27 atomic% grafted nitrogen, optionally 27 to 28 atomic% grafted nitrogen, optionally 28 It comprises a carbon or silicon compound containing up to 29 atomic percent grafted nitrogen, optionally 29 to 30 atomic percent grafted nitrogen.

[0382] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface, when measured by X-ray photoelectron spectroscopy (XPS), comprises 0 to 30 atomic% grafted nitrogen, optionally 0 to 20 atomic% grafted nitrogen, optionally 0.1 to 30 atomic% grafted nitrogen, optionally 0.1 to 20 atomic% grafted nitrogen, optionally 0.1 to 10 atomic% grafted nitrogen, and optionally 0.1 to 1 atomic% grafted nitrogen, optionally 1 to 2 atomic% grafted nitrogen, optionally 2 to 3 atomic% grafted nitrogen, optionally 3 to 4 atomic% grafted nitrogen, optionally 4 to 5 atomic% grafted nitrogen, optionally 5 to 6 atomic% grafted nitrogen, optionally 6 to 7 atomic% grafted nitrogen, optionally 7 to 8 atomic% grafted nitrogen, optionally 8 to 9 atomic% grafted nitrogen, optionally 9 to 10 atomic% grafted nitrogen, optionally 10 to 11 atomic% grafted nitrogen, optionally 11 to 12 atomic% grafted nitrogen, optionally 12 to 13 atomic% grafted nitrogen, optionally 13 to 14 atomic% grafted nitrogen, optionally 14 to 15 atomic% Grafted nitrogen, optionally 15 to 16 atomic% grafted nitrogen, optionally 16 to 17 atomic% grafted nitrogen, optionally 17 to 18 atomic% grafted nitrogen, optionally 18 to 19 atomic% grafted nitrogen, optionally 19 to 20 atomic% grafted nitrogen, optionally 20 to 21 atomic% grafted nitrogen, optionally 21 to 22 atomic% grafted nitrogen, optionally 22 to 23 atomic% grafted nitrogen, optionally 23 to 24 atomic% grafted nitrogen, optionally 24 to 25 atomic% grafted nitrogen, optionally 25 to 26 atomic% grafted nitrogen, optionally 26 to 27 atomic% grafted nitrogen, optionally 27 to 28 atomic% grafted nitrogen, optionally 28 It further comprises up to 29 atomic percent grafted nitrogen, optionally up to 29 to 30 atomic percent grafted nitrogen.

[0383] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a grafted hydrogen bonding acceptor functional group, e.g., -N bonded to carbon or silicon in each case when measured by X-ray photoelectron spectroscopy (XPS). + Includes one or more of -, -N-, =O, -O-, -O2, -O3, or ≡=N.

[0384] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is a polar grafted species, optionally, C=O (carbonyl), COC (ether), CNC (amine), CN, when measured by X-ray photoelectron spectroscopy (XPS). + -C (ammonium), CO2 (carboxyl), CO3, Si=O, Si-O-Si, Si-N-Si, Si-N + It includes carbon or silicon compounds modified from one or more of -Si, SiO2, SiO3, C≡=N, Si≡=N, or combinations of two or more of these.

[0386] Grafted bell

[0387] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface comprises a hydrocarbon modified with a polar grafted species, C=O (carbonyl), COC (ether), CNC (amine), CO2 (carboxyl), CO3, N-C3, N + The total atomic ratio of carbon sources forming combinations of two or more of C4, C≡=N, or these grafted species is 1 to 40%, optionally 5 to 30%, and optionally 10 to 20% of the total atomic ratio of carbon bonded to carbon or hydrogen in the substrate.

[0388] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface comprises a silicon compound modified with a polar grafted species, Si=O, Si-O-Si, Si-N-Si, SiO2, SiO3, N-Si3, N + The total atomic ratio of silicon forming Si4, Si≡=N, or a combination of two or more of these is 1 to 40%, optionally 5 to 30%, and optionally 10 to 20% of the total atomic ratio of silicon bonded to oxygen in the substrate.

[0389] In one aspect of the description in any embodiment, the total atomic ratio of carbon forming C=O (carbonyl), COC (ether), CNC (amine), CO2 (carboxyl), or CO3, or a combination of two or more of these, is 1 to 40%, optionally 5 to 30%, and optionally 10 to 20% of the total atomic ratio of carbon bonded to carbon or hydrogen in the description.

[0390] In one aspect of the description in any embodiment, the total atomic ratio of carbon forming COC (ether) or CNC (amine) or a combination of both is 1 to 40%, optionally 5 to 30%, and optionally 10 to 20% of the total atomic ratio of carbon bonded to carbon or hydrogen in the description.

[0391] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a contact angle with distilled water of 0° to 90°, optionally 20° to 80°, optionally 40° to 80°, optionally 50° to 70°, and optionally 55° to 65°.

[0392] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a biomolecule recovery percentage of at least 40%, optionally at least 45%, optionally at least 50%, optionally at least 55%, optionally at least 60%, optionally at least 65%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, optionally at least 90%, and optionally at least 95%.

[0393] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is the lumen surface of the vessel.

[0394] In one aspect of the description in any embodiment, the percentage of biomolecule recovered is determined for at least one of mammalian serum albumin; bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN); egg white ovotransferrin (conalbumin); membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin; pharmaceutical protein; blood or blood component protein; and any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins.

[0395] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface comprises a thermoplastic material, for example, a thermoplastic resin, for example, an injection-molded thermoplastic resin.

[0396] In one embodiment of the description in any embodiment, the converted and optionally conditioned contact surface comprises a hydrocarbon, e.g., an olefin polymer, polypropylene (PP), polyethylene (PE), a cyclic olefin copolymer (COC), a cyclic olefin polymer (COP), polymethylpentene, polystyrene, hydrogenated polystyrene, polycyclohexylethylene (PCHE), or a combination of two or more of these. The converted and optionally conditioned contact surface comprises optionally heteroatom-substituted hydrocarbon polymers, e.g., polyester, polyethylene terephthalate, polyethylene naphthalate, polybutylene terephthalate (PBT), polyvinylidene chloride (PVdC), polyvinyl chloride (PVC), polycarbonate, polylactic acid, epoxy resin, nylon, polyurethane polyacrylonitrile, polyacrylonitrile (PAN), ionomer resin, Surlyn® ionomer resin, or any combination, composite, or blend of any two or more of the above materials.

[0397] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is PECVD-deposited SiO x C y H z or SiN x C y H z It is a coating or layer, where x is about 0.5 to about 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is about 0.6 to about 3 as measured by XPS, and z is about 2 to about 9 as measured by Rutherford backscatter spectroscopy (RBS).

[0398] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is SiO x(where x is about 1.5 to about 2.9 as measured by XPS), optionally a barrier coating or layer of an oxide or nitride of an organometallic precursor that is a compound of a metal element of Group III and / or Group IV of the periodic table, for example, Group III is boron, aluminum, gallium, indium, thallium, scandium, yttrium, or lanthanum (aluminum and boron preferred), and Group IV is silicon, germanium, tin, lead, titanium, zirconium, hafnium, or thorium (silicon and tin preferred).

[0399] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is a contact surface of a laboratory article. For example, the converted and optionally conditioned contact surface may be, without limitation, a contact surface of a microplate, centrifuge tube, pipette tip, well plate, microwell plate, ELISA plate, microtiter plate, 96-well plate, 384-well plate, vial, bottle, jar, syringe, cartridge, blister package, ampoule, vacuum blood collection tube, specimen tube, centrifuge tube, or chromatography vial.

[0400] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface is the lumen surface of the vessel.

[0401] In one aspect of the description of any embodiment, the converted and optionally conditioned contact surface is in contact with an aqueous protein. In one aspect of the description of any embodiment, the aqueous protein comprises: mammalian serum albumin, e.g. bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g. blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g. hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin, and pharmaceutical-grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins; Or a combination of two or more of these.

[0402] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage higher than the protein recovery percentage of the unconditioned and unconverted surface, for at least one of bovine serum albumin (BSA); fibrinogen (FBG); transferrin (TFN), e.g., blood serotransferrin (or siderophyllin also known as transferrin); lactotransferrin (lactoferrin); milk transferrin; egg white ovotransferrin (conalbumin); and membrane-associated melanotransferrin; protein A (PrA); protein G (PrG); protein A / G; protein L; insulin, e.g., hexameric insulin, monomeric insulin, porcine insulin, human insulin, recombinant insulin and pharmaceutical grade insulin; pharmaceutical proteins; blood or blood component proteins; or any recombinant form, variant, full-length precursor, signal peptide, propeptide, or mature variant of these proteins.

[0403] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a higher percentage of protein recovery for bovine serum albumin (BSA) with an atomic mass of 66,000 daltons on a NUNC® 96-well round bottom plate than the percentage of protein recovery for an unconditioned and unconverted surface when following the protocol of this specification.

[0404] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for BSA on a NUNC® 96-well round bottom plate greater than 70%, optionally greater than 80%, optionally greater than 90%, and optionally less than or equal to 100% when following the protocol of this specification.

[0405] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for fibrinogen (FBG) with an atomic mass of 340,000 daltons on a NUNC® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted surface.

[0406] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for FBG on a NUNC® 96-well round bottom plate of greater than 20%, optionally greater than 40%, optionally greater than 60%, optionally greater than 80%, and optionally less than or equal to 84% when following the protocol of this specification.

[0407] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours on a NUNC® 96-well round bottom plate for transferrin (TFN) with an atomic mass of 80,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0408] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for TFN on a NUNC® 96-well round bottom plate of greater than 60%, optionally greater than 65%, optionally greater than 69%, and optionally less than or equal to 70% when following the protocol of this specification.

[0409] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for protein A (PrA) with an atomic mass of 45,000 daltons on a NUNC® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted surface.

[0410] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for PrA on a NUNC® 96-well round bottom plate of greater than 9%, optionally greater than 20%, optionally greater than 40%, optionally greater than 60%, and optionally less than or equal to 67% when following the protocol of this specification.

[0411] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for protein G (PrG) with an atomic mass of 20,000 daltons on a NUNC® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted surface.

[0412] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for PrG on a NUNC® 96-well round bottom plate of greater than 12%, optionally greater than 20%, optionally greater than 40%, optionally greater than 60%, optionally greater than 80%, and optionally less than or equal to 90% when following the protocol of this specification.

[0413] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for bovine serum albumin (BSA) with an atomic mass of 66,000 daltons on an Eppendorf LoBind® low-protein binding 96-well round-bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface. LoBind® is a trademark of Eppendorf AG, Hamburg, Germany.

[0414] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage of more than 95% at 24 hours on an Eppendorf LoBind® 96-well round bottom plate with respect to BSA when following the protocol of this specification.

[0415] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has a protein recovery percentage at 24 hours for fibrinogen (FBG) with an atomic mass of 340,000 daltons on an Eppendorf LoBind® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted surface.

[0416] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage of more than 72% at 24 hours for FBG on an Eppendorf LoBind® 96-well round bottom plate when following the protocol of this specification.

[0417] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours on an Eppendorf LoBind® 96-well round bottom plate for transferrin (TFN) with an atomic mass of 80,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0418] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage of more than 69% at 24 hours for TFN on an Eppendorf LoBind® 96-well round bottom plate when following the protocol of this specification.

[0419] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for protein A (PrA) with an atomic mass of 45,000 daltons when following the protocol of this specification on an Eppendorf LoBind® 96-well round bottom plate that is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0420] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for protein G (PrG) with an atomic mass of 20,000 daltons when following the protocol of this specification on an Eppendorf LoBind® 96-well round bottom plate that is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0421] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage of more than 96% at 24 hours for PrG on an Eppendorf LoBind® 96-well round bottom plate when following the protocol of this specification.

[0422] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for bovine serum albumin (BSA) with an atomic mass of 66,000 daltons on a GRIENER® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0423] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage of greater than 60% and optionally less than or equal to 86% at 24 hours on a GRIENER® 96-well round bottom plate with respect to BSA when following the protocol of this specification.

[0424] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for fibrinogen (FBG) with an atomic mass of 340,000 daltons on a GRIENER® 96-well round bottom plate when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0425] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for FBG on a GRIENER® 96-well round bottom plate of greater than 50%, optionally 65% ​​or less, when following the protocol of this specification.

[0426] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours on a GRIENER® 96-well round bottom plate for transferrin (TFN) with an atomic mass of 80,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0427] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for TFN on a GRIENER® 96-well round bottom plate greater than 50%, optionally 60% or less, when following the protocol of this specification.

[0428] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for protein A (PrA) with an atomic mass of 45,000 daltons when following the protocol of this specification on a GRIENER® 96-well round bottom plate that is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0429] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for PrA on a GRIENER® 96-well round bottom plate greater than 25%, optionally 56% or less.

[0430] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage at 24 hours for protein G (PrG) with an atomic mass of 20,000 daltons when following the protocol of this specification on a GRIENER® 96-well round bottom plate that is higher than the protein recovery percentage of an unconditioned and unconverted surface.

[0431] In one aspect of the description in any embodiment, the treated contact surface has a protein recovery percentage of PrG at 24 hours on a GRIENER® 96-well round bottom plate greater than 60%, optionally 75% or less, when following the protocol of this specification.

[0432] In one aspect of the description in any embodiment, the carbon or silicon compound essentially comprises polypropylene, optionally a polypropylene homopolymer.

[0433] In one aspect of the description in any embodiment, the treated polypropylene contact surface has a protein recovery percentage for bovine serum albumin (BSA) with an atomic mass of 66,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted polypropylene surface.

[0434] In one aspect of the description in any embodiment, the treated polypropylene contact surface has a protein recovery percentage for cellulose fiber (FBG) with an atomic mass of 340,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted polypropylene surface.

[0435] In one aspect of the description in any embodiment, the treated polypropylene contact surface has a protein recovery percentage with respect to transferrin (TFN) having an atomic mass of 80,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of an unconditioned and unconverted polypropylene surface.

[0436] In one aspect of the description in any embodiment, the treated polypropylene contact surface has a protein recovery percentage for protein A (PrA) with an atomic mass of 45,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted polypropylene surface.

[0437] In one aspect of the description in any embodiment, the treated polypropylene contact surface has a protein recovery percentage for protein G (PrG) with an atomic mass of 20,000 daltons when following the protocol of this specification, which is higher than the protein recovery percentage of the unconditioned and unconverted polypropylene surface.

[0438] In one aspect of the description in any embodiment, the carbon or silicon compound essentially comprises polypropylene, and the converted and optionally conditioned contact surface has any one or more of the following characteristics:

[0439] ● Water contact angle of 0 to 90 degrees;

[0440] ● When quantified by XPS, compared to the carbon or silicon compound before treatment, a smaller proportion of hydrogen bond donor functional groups, e.g., -OH, -NH, -N-H2, -N, of the total atomic ratio of carbon bonded to carbon or hydrogen in the substrate. + H3, or a combination of two or more of these;

[0441] ● When quantified by XPS, compared to the carbon or silicon compound before treatment, the total atomic ratio of carbons bonded to carbon or hydrogen in the substrate, with a higher number of hydrogen bond acceptor functional groups, e.g., C=O (carbonyl), COC (ether), CNC (amine), CN + -C (ammonium), CO2 (carboxyl), or CO3, or a combination of two or more of these; and

[0442] ● Charge-neutral or nearly charge-neutral, e.g., when quantified using a static sensor—3M Static Sensor 718—2 kilovolts per inch (2 kV / in, 5 kV / cm), optionally less than 3 kV / cm, optionally less than 2 kV / cm, optionally less than 1 kV / cm, converted and optionally conditioned electrostatic charge accumulation on a contact surface.

[0443] In one aspect of the substrate in any embodiment, the converted and optionally conditioned contact surface, when quantified by XPS, has hydrogen bond donor functional groups, e.g., -OH, -NH, -N-H2, -N, of which the total atomic ratio of carbon bonded to carbon or hydrogen in the substrate is lower than that of the carbon or silicon compound before treatment. + H3, or a combination of two or more of these.

[0444] In one aspect of the substrate in any embodiment, the converted and optionally conditioned contact surface has hydrogen bond acceptor functional groups, e.g., C=O (carbonyl), COC (ether), CNC (amine), C-N+-C (ammonium), CO2 (carboxyl), or CO3, of the total atomic ratio of carbon bonded to carbon or hydrogen in the substrate, which is greater than that of the carbon or silicon compound before treatment when quantified by XPS.

[0445] In one aspect of the description in any embodiment, the converted and optionally conditioned contact surface has charge-neutral or nearly charge-neutral, for example, quantified as above, 2 kilovolts per inch (2 kV / in, 5 kV / cm), optionally less than 3 kV / cm, optionally less than 2 kV / cm, and optionally less than 1 kV / cm.

[0447] PECVD coating and layer

[0448] Another method for reducing biomolecule attachment is to use as a contact surface, (i) a barrier coating or layer having an atomic ratio, SiOx (where x is about 0.5 to about 2.4) or atomic ratio SiO x C y H z The present invention provides a pH protective coating or layer having a pH of about 0.5 to about 2.4 and y of about 0.6 to about 3, each of which is measured by XPS. Such coatings and methods for forming them on a substrate are described in WO2014US23813, which is incorporated herein by reference.

[0450] Work example

[0451] Various aspects will be illustrated in more detail with reference to the following examples, but it should be understood that the more detailed first embodiment is not to be considered limited thereto.

[0453] Test of all implementation examples

[0454] Except as otherwise indicated in the examples, plates in all embodiments were tested using the following protocol:

[0455] Objective: The objective of this experiment was to determine the amount of protein binding over time to a surface-coated microtiter plate (microtiter plates are also referred to herein as "microplates" or sometimes as "plates" of the type having wells; all three terms have the same meaning herein).

[0456] Material: BIOTEK ® Synergy H1 Microplate Reader and BIOTEK Gen5 ® Software, MILLIPORE ® MILLI-Q ® Water System (sold by Merck KGAA, Darmstadt, Germany), MILLIPORE ® Direct Detect Spectrometer, ALEXA FLUOR ®488 labeled protein (bovine serum albumin (BSA), fibrinogen (FBG), transferrin (TFN), protein A (PrA), and protein G (PrG) sold by Molecular Probes, Inc., Eugene, Oregon, USA), 10X phosphate-buffered saline (PBS), NUNC ® Black 96-well optical bottom plate, 1 L plastic bottle, 25 to 100 mL glass beaker, aluminum foil, 1 to 10 mL pipette, 100 to 1000 µL pipette, 0.1 to 5 µL pipette, 50 to 300 µL multichannel pipette.

[0457] One or more selected proteins among those listed above were tested on a single surface-coated microplate. Each protein was tested using ALEXA FLUOR ® Received as fluorescently labeled powder labeled with 488:

[0458] ● 5 mg of BSA: 66,000 Da

[0459] ● 5 mg of FBG: 340,000 Da

[0460] ● 5 mg TFN: 80,000 Da

[0461] ● 1 mg PrA: 45,000 Da

[0462] ● 1 mg of PrG: 20,000 Da

[0463] Immediately after receiving, each protein vial was wrapped in aluminum foil for additional protection from light, labeled accordingly, and stored in a freezer.

[0464] A 1X PBS (phosphate buffer) solution was prepared from a 10X PBS stock solution: after adding 100 mL of 10X PBS to a 1 L plastic bottle, MILLIPORE ®900 mL of distilled water from the Q-pod was added to form 1X PBS. Using a 100 to 1000 µL pipette, 1000 µL of 1X PBS was individually pipetted into each protein vial to create the protein solution. Then, each vial was inverted and vortexed to thoroughly mix the solution.

[0465] Next, mill each protein ® Accurate protein concentrations were obtained by testing on a Direct Detect device. Using a 0.1 to 5 µl pipette, 2 µl of PBS sample was placed on the first spot of the Direct Detect reading card and marked as blank in the software. Subsequently, 2 µl of the first protein sample was placed on the remaining three spots and marked as samples. After reading the card, the average of the three protein concentrations was recorded in mg / mL. This process was repeated for the remaining four proteins. The protein solutions were then stored in a refrigerator.

[0466] A standard curve was constructed with 1X PBS for each protein. The standard curve started at 25 nM, and serial 2x dilutions were performed to obtain one or more of the other concentrations tested, e.g., 12.5 nM, 6.25 nM, 3.125 nM, and 1.5625 nM. In some cases, an additional dilution to 0.5 nM was also prepared. The 12.5 nM solution prepared from the standard curve was used for the test.

[0467] Once dilutions for all proteins to be tested were completed, a standard curve was constructed for each protein and tested as follows. Five rows of 25 to 100 mL glass beakers were arranged. Each beaker was wrapped in aluminum foil, and the protein name and the concentration of the solution within the beaker were labeled for the corresponding curve. Column 1 was the standard curve for BSA; Column 2 was the standard curve for FBG; Column 3 was the standard curve for TFN; Column 4 was the standard curve for PrA; and Column 5 was the standard curve for PrG. Accordingly, Column 1 was labeled as follows: BSA 25 nM, BSA 12.5 nM, BSA 6.25 nM, BSA 3.125 nM, BSA 1.56 nM.

[0468] After plotting a standard curve, the test was performed using a microplate reader, and then the process was carried out by plotting and testing the next standard curve.

[0469] BIOTEK ® Synergy H1 Microplate Reader and BIOTEK Gen5 ® Software was used for analysis.

[0470] After the first standard curve was prepared, it was ready to be tested on Synergy H1. Using a 50 to 300 µL multichannel pipette, 200 µL of 1X PBS was pipetted into wells A1 to A4 of a black optical bottom microplate. Subsequently, 200 µL of 25 nM solution was pipetted into wells B1 to B4, 200 µL of 12.5 nM solution was pipetted into wells C1 to C4, 200 µL of 12.5 nM solution was pipetted into wells D1 to D4, 200 µL of 12.5 nM solution was pipetted into wells E1 to E4, 200 µL of 12.5 nM solution was pipetted into wells F1 to F4, and 200 µL of 12.5 nM solution was pipetted into wells G1 to G4. Using a similar procedure, the wells were filled with different dilutions of the protein solution.

[0471] Once the microplate was filled with solution, it was wrapped in aluminum foil and labeled with sections and time points.

[0472] After 1.5 hours, a hole was punctured in the aluminum foil using a 50 to 300 µL multichannel pipette, and 200 µL of BSA solution was pipetted from the well of the 1.5-hour column (Column 1) into a black optical bottom microplate. The black microplate was placed in a microplate tray. Subsequently, the other four proteins were read in the same manner by initiating their corresponding experiments. The same procedure was performed after 2.5 hours, 4.5 hours, and 24 hours. After the reading at 24 hours, "Plate → Export" was selected from the menu bar. An Excel spreadsheet appeared, which could then be saved to a desired location with a desired name.

[0473] BIOTEK Gen5 ®Using data generated by the software, the average of the 12.5 nM solution concentrations from both the standard curve and SPL1 was calculated. The average of the concentrations in the four wells at 1.5 hours was calculated. This was then performed for 2.5 hours, 4.5 hours, and 24 hours. Subsequently, the average concentration at each time point was divided by the initial average concentration of 12.5 nM and multiplied by 100 to obtain the percentage recovery at each time point:

[0474] % Recovery rate at 1.5 hours = [Average BSA 1.5 hours] / [Average 12.5 nM solution] * 100

[0475] In another aspect, either embodiment (i) or embodiment (ii) relates to a method for applying a non-specific biomolecule adsorption and / or binding-resistant surface coating to a substrate, for example, by using chemical vapor deposition (CVD), which is characterized by non-binding properties with respect to biomolecules. In any embodiment, the substrate may comprise glass or a thermoplastic resin, for example, a polymer, for example, a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer, or any combination of two or more of these.

[0476] Non-specific biomolecule adsorption and / or binding resistance coating

[0477] In a primary aspect thereof, either embodiment (i) or embodiment (ii) provides a surface coating of a container that is resistant to non-specific biomolecule adsorption and / or binding. Such a surface coating that is resistant to non-specific biomolecule adsorption and / or binding is advantageously prepared by performing a method such as the following.

[0478] Surface modification was performed under various conditions, for example, on a polypropylene microplate (NUNC, 96 wells, 0.5 ml, round bottom). For example, either embodiment (i) or embodiment (ii) involves two stages, namely, for example, hydroxylated plastic or SiO x - It may include a substrate conditioning stage for providing a coated glass surface, ii) a copolymerization stage for obtaining a surface coating resistant to non-specific biomolecule adsorption and / or binding.

[0479] The process of either embodiment (i) or embodiment (ii) yields a non-specific biomolecule adsorption and / or non-specific binding-resistant surface coating. For example, the present invention provides a method for providing a non-specific biomolecule adsorption and / or binding-resistant surface coating surface that exhibits low or non-binding properties of biomolecules. The present invention also provides a method for providing a non-specific biomolecule adsorption and / or non-specific binding-resistant surface coating surface that inhibits the adsorption of biomolecules. In a preferred embodiment, the non-specific biomolecule adsorption and / or binding-resistant coating may be covalently bonded to a prepared substrate, but may be bonded to a prepared substrate in a different manner.

[0480] copolymerizable siloxane monomer

[0481] Embodiment (i) is, for example, (3-acryloxypropyl)trimethoxysilane; methacryloxypropyltrimethoxysilane; n-(3-acryloxy-2-hydroxypropyl)-3-aminopropyltriethoxysilane; o-(methacryloxyethyl)-n-(triethoxysilylpropyl)urethane; n-(3-methacryloxy-2-hydroxypropyl)-3-aminopropyltriethoxysilane; methacryloxymethyltriethoxysilane; methacryloxymethyltrimethoxysilane; methacryloxypropyltriethoxysilane; (3-acryloxypropyl)methyl-dimethoxysilane; (methacryloxymethyl)methyl-dimethoxysilane; (methacryloxymethyl)methyl-dimethoxysilane; methacryloxypropylmethyldimethoxysilane; methacryloxypropylmethyldimethoxysilane; Copolymerizable siloxane monomers such as methacryloxypropyl dimethyl ethoxysilane are used.

[0482] copolymerizable epoxy monomer

[0483] For example, in embodiment (ii), copolymerizable epoxy monomers may be used. Non-limiting examples of polymerizable epoxy monomers include glycidyl acrylate, glycidyl methacrylate (GMA), (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, and (oxiran-2-yl)methyl It includes 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, and (3,3-dimethyloxiran-2-yl)methyl acrylate. These monomers may be used alone or as a mixture thereof.

[0484] Silylamine coupling agent

[0485] In embodiment (ii), a silylamine coupling agent may be used. Non-limiting examples include 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, M-aminophenyltrimethoxysilane, P-aminophenyltrimethoxysilane, O-aminophenyltrimethoxysilane, 3-aminopropyltris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(M-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)]aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, bis(triethoxysilylpropyl)amine,Bis(trimethoxysilylpropyl)amine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis[(3-trimethoxysilyl)propyl]-ethylenediamine, bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysila-cyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysila-cyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclo-octane, N-methyl-aza-2,2,4-trimethylsila-cyclopentane, and It includes 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane. These reagents may be used alone or as a mixture thereof.

[0486] copolymerizable zwitterionic monomer

[0487] Either embodiment (i) or embodiment (ii) may use, for example, a copolymerizable zwitterionic monomer. Non-limiting examples of copolymerizable monomers are, for example, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate (MPC), 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate (aka = 2-methacryloyloxyethyl phosphorylcholine; 2-(methacryloyloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloyloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacrylamido)ethyl 2-(dimethylammonio)ethyl phosphate ester; 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate,2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, Includes 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyoxy)ethyl-2'-(trimethylammonio)ethyl phosphate, ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, beta-carboxyethyl-3,3-dimethylammonium ethyl methacrylate, and sulfopropyl-3,3-dimethylammonium ethyl methacrylate. These monomers may be used alone or as a mixture thereof.

[0488] Examples of radical polymerizable monomers useful in embodiment (i) are also, for example, hydroxyalkyl (meth)acrylate monomers, e.g., 2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate; polyalkylene glycol (meth)acrylate monomers, e.g., diethylene glycol mono(meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, methoxydiethylene glycol (meth)acrylate, methoxypolyethylene glycol (meth)acrylate, and methoxypolypropylene glycol (meth)acrylate; Omega-carboxy(meth)acrylates, for example, monohydroxyethyl(meth)acrylate of phthalate, monohydroxyethyl(meth)acrylate of hexahydrophthalate, omega-carboxy-polycaprolactone (n=2 to 5) mono(meth)acrylate, and (meth)acryloyloxyethyl succinate; may include N-vinyl-2-pyrrolidone, vinylpyridine, (meth)acrylamide, (meth)acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid, dimethylaminoethyl(meth)acrylate, diethylaminoethyl(meth)acrylate, maleic anhydride, and glyco-2-hydroxyethyl monomethacrylate (GEMA).

[0489] For embodiment (i), the copolymer may be obtained by radical polymerization of a monomer composition containing at least one monomer and optionally one or more monomers, for example, in a solvent, optionally in the presence of a polymerization initiator. Radical polymerization may be carried out in a system while replacing the atmosphere with an inert gas, for example, nitrogen, argon, carbon dioxide, or helium.

[0490] For embodiment (ii), the copolymer may be obtained by radical polymerization of a monomer composition containing at least one copolymerizable zwitterionic monomer, optionally one or more copolymerizable zwitterionic monomers, and at least one copolymerizable epoxy monomer, optionally one or more copolymerizable epoxy monomers, in a solvent, for example, optionally in the presence of a polymerization initiator. The polymerization may be carried out in a system while replacing the atmosphere with an inert gas, for example, nitrogen, argon, carbon dioxide, or helium.

[0491] With respect to either embodiment (i) or embodiment (ii), the polymerization initiator is not limited. Conventional polymerization initiators for radical polymerization may be used. Examples of initiators are organic peroxides, e.g., t-butyl peroxypivalate, t-butyl peroxyneodecanoate, t-butyl peroxy-2-ethylhexanoate, t-butyl peroxyacetate, 1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, succinic acid peroxide, benzoyl peroxide, 3,5,5-trimethylhexanoyl peroxide, lauroyl peroxide, tertiary-butyl hydroperoxide, tertiary-butyl peracetate, cumene hydroperoxide, 2,5-di(tertiary-butylperoxy)-2,5-dimethyl-3-hexine, dicumyl peroxide, 2,5-bis(tertiary-butylperoxy)-2,5-dimethylhexane, 2,4-pentanedione peroxide, 1,1-Bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane, 1,1-Bis(tert-butylperoxy)cyclohexane, benzoyl peroxide, 2-butanone peroxide, di-tert-butyl peroxide, lauroyl peroxide, tert-butyl peroxybenzoate, tert-butylperoxy and 2-ethylhexyl carbonate;,; Azo compounds, e.g., 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2-amidinopropane)hydrochloride, dimethyl 2,2'-azobis(isobutyrate), 2,2'-azobis(2,4-dimethylvaleronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), 2,2'-azobis(2-methyl-N-(2-hydroxyethyl)-propionamide, 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobis(2-methylpropionamidine), and 2,2'-azobis(2-methylpropionitrile); inorganic radical initiators, e.g., potassium persulfate, sodium persulfate, ammonium persulfate, persulfate-hydrogen sulfite systems, and It may include hydroxymethasulfinic acid. Such polymerization initiators may be used alone or as a mixture thereof.

[0492] For either embodiment (i) or embodiment (ii), the amount of polymer used is preferably 0.001 to 10 parts by weight per 100 parts by weight of the total amount of monomer, and more preferably 0.01 to 5 parts by weight.

[0493] For either embodiment (i) or embodiment (ii), the solvent for producing the copolymer is not particularly limited, provided that the solvent is a solvent that dissolves the monomer provided as a structural unit of the copolymer and does not react with the copolymer. The solvent may be a mixed solvent. The solvent may be, for example, water, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, methylene chloride, 1,2-dichloroethane, etc., or a combination thereof.

[0494] Substrate surface manufacturing

[0495] Either embodiment (i) or embodiment (ii) provides for the preparation of a substrate surface to obtain a prepared substrate surface. The prepared substrate surface may be prepared, for example, by oxygen plasma treatment on the plain surface of the vessel to provide a hydroxylated plastic surface, such as a polypropylene microplate. For embodiment (i), alternatively, in a specific embodiment, the hydroxyl-functional surface may be formed from an O2 / plasma reaction, for example, on a carbon-based polymer surface (AC) forming a C-OH moiety, or on a silicon-based (SiO2 or silicon) surface (ASi) forming a Si-OH moiety. Additionally, the hydroxyl-functional surface may be inherent in (B) the initial surface, such as a polymer, such as polyvinyl alcohol (PVOH) or a silicon-based polymer surface (SiO2 or silicon). Accordingly, the O2 / plasma surface fabrication method may be selective when an intrinsic hydroxyl moiety is present on the surface.

[0496] Either embodiment (i) or embodiment (ii) is SiO x - To form a coated glass surface, for example, SiO x Provides the preparation of a substrate surface by deposition. SiO x The coated surface may be prepared, for example, by plasma-enhanced chemical vapor deposition (PECVD). PECVD equipment and methods for depositing any coating defined herein, for example, a coating comprising silicon, oxygen, and optionally carbon, are disclosed, for example, in WO2013 / 071138 published on May 16, 2013, which is incorporated herein by reference.

[0497] Another example of a chemical vapor deposition process useful in any embodiment of a type of PECVD is plasma impulse chemical vapor deposition (PICVD). Suitable equipment and processing conditions for PICVD can be found, for example, in US7399500.

[0498] Another example of a chemical vapor deposition process useful in any embodiment is pulsed plasma enhanced chemical vapor deposition (PPECVD). Suitable apparatus and processing conditions for PPECVD can be identified, for example, in the literature [SJLimb, KKSLau, DJEdell, EFGleason, KKGleason, Molecular Design Of Fluorocarbon Film Architecture By Pulsed Plasma Enhanced And Pyrolytic Chemical Vapor Deposition, PLASMA POLYMERIZATION 4 1999 21-32], which is incorporated herein by reference.

[0499] Another example of a chemical vapor deposition process useful in either embodiment (i) or embodiment (ii) is pyrolytic chemical vapor deposition (PCVD). Suitable apparatus and processing conditions for PCVD can be identified, for example, in the literature [SJLimb, KKSLau, DJEdell, EFGleason, KKGleason, Molecular Design Of Fluorocarbon Film Architecture By Pulsed Plasma Enhanced And Pyrolytic Chemical Vapor Deposition, PLASMA POLYMERIZATION 4 1999 21-32], which is incorporated herein by reference.

[0500] Another example of a useful chemical vapor deposition process in embodiment (i) is the pyrolysis of a precursor, e.g., hexafluoropropylene oxide. Suitable apparatus and processing conditions for pyrolysis can be identified, for example, in the literature [J. Wang, X. Song, R. Lia, J. Shen, G. Yang, H. Huang, Fluorocarbon Thin Film With Superhydrophobic Property Prepared By Pyrolysis Of Hexafluoropropylene Oxide, APPLIED SURFACE SCIENCE 258 2012 9782-9785], which is incorporated herein by reference.

[0501] Preferably, in either embodiment (i) or embodiment (ii), PECVD is used to generate a barrier layer on a substrate to form a coated surface having low- or non-binding properties and / or resistance to biomolecular adsorption. A method for applying a coating using PECVD is taught in U.S. Patent No. 7,985,188, the full text of which is incorporated herein by reference.

[0502] In the context of either embodiment (i) or embodiment (ii), the following PECVD method is generally applied to provide an initial barrier layer, which comprises the following steps: (a) providing, in the case of embodiment (i), a gaseous reactant containing a precursor, or in the case of embodiment (ii), a silylamine coupling agent (each as defined herein) and optionally O2 near the substrate surface; (b) generating a plasma from the gaseous reactant to form a coating on the substrate surface by plasma-enhanced chemical vapor deposition (PECVD). In one embodiment of embodiment (i), the barrier coating may be either a silazane or a siloxane. In one embodiment of embodiment (ii), the barrier coating will be a silylamine.

[0503] In either embodiment (i) or embodiment (ii), the coating feature is advantageously set by one or more of the following conditions: plasma properties, pressure to which the plasma is applied, power applied to generate the plasma, pressure and relative amount of O2 in the gaseous reactants, plasma volume, and in the case of embodiment (i), the precursor, or in the case of embodiment (ii), the silyl amine coupling agent. Optionally, the coating feature is set by the presence and relative amount of O2 in the gaseous reactants and / or power applied to generate the plasma.

[0504] In an additional preferred embodiment of either embodiment (i) or embodiment (ii), the plasma is generated under reduced pressure (compared to ambient or atmospheric pressure). Optionally, the reduced pressure is less than 300 mTorr, optionally less than 200 mTorr, and even optionally less than 100 mTorr.

[0505] PECVD of either embodiment (i) or embodiment (ii) is performed by supplying energy to a gaseous reactant containing a precursor, optionally at a frequency in microwave or radio frequency, and optionally to an electrode output at radio frequency. The radio frequency preferred for performing one embodiment will also be referred to as "RF frequency." A typical radio frequency range for performing the invention is a frequency of 10 kHz to less than 300 MHz, optionally 1 to 50 MHz, and even optionally 10 to 15 MHz. For example, a frequency of 13.56 MHz is preferred, which is a government-approved frequency for performing PECVD operations. The invention may be performed at other frequencies, such as, for example, 27.12 MHz or 40.68 MHz.

[0506] For either embodiment (i) or embodiment (ii), using an RF power source compared to a microwave source has several advantages: Since the RF operates at a low output, the substrate / container is heated less. Since the focus of the present invention is to form a plastic coating on a plastic substrate, a low processing temperature is desired to prevent melting / deformation of the substrate. To prevent substrate overheating when using microwave PECVD, microwave PECVD is applied in short bursts by pulsed output. Pulsed output extends the cycle time for coating, which is not desired in the present invention. Higher frequency microwaves can also cause off-gassing of volatile substances, such as residual water, oligomers, and other materials, from the plastic substrate. Such off-gassing can interfere with the PECVD coating. A major problem associated with using microwaves for PECVD is delamination of the coating from the substrate. Delamination occurs because the microwaves alter the surface of the substrate before the coating layer is deposited. To reduce the possibility of delamination, an interfacial coating layer was developed to achieve good bonding between the coating and the substrate during microwave PECVD. Since there is no risk of delamination, such an interfacial coating layer is not required with RF PECVD. Finally, the barrier layer according to the present invention is applied using advantageously low power. RF power operates at low power and provides greater control over the PECVD process compared to microwave power. Nevertheless, although microwave power is less desirable, it is available under suitable process conditions, such as, for example, 300 MHz to 300 GHz.

[0507] Additionally, for all PECVD methods described herein in either embodiment (i) or embodiment (ii), there is a specific correction between the output (watts) used to generate the plasma and the volume of the lumen where the plasma is generated. Typically, the lumen is the lumen of the vessel coated according to the present invention. The RF output must be adjusted to the volume of the vessel when the same electrode system is used. Immediately after all other parameters of the PECVD coating method, excluding the composition of the gaseous reactants, e.g., the ratio of the precursor to O2, and the output, these will typically not change when the geometry of the vessel is maintained and only its volume changes. In this case, the output will be directly proportional to the volume. Accordingly, starting from the ratio of output to volume provided by this specification, the output applied to achieve the same or similar coating in a vessel of the same geometry, excluding different sizes, can be easily determined.

[0508] A precursor is provided for embodiment (i). Preferably, the precursor is an organosilicon compound (also referred to as "organosilicon precursor" below), more preferably, for example, a linear siloxane, monocyclic siloxane, polycyclic siloxane, polysilsesquioxane, alkyl trimethoxysilane, trialkoxysilane, silazane analogs of any of these precursors (i.e., linear silazane, monocyclic silazane, polycyclic silazane, polysilsesquioxane), silazane, trimethylsilazane, trialkylsilazane, tetramethylsilazane, and any combination of two or more of these precursors. The precursor is applied to a substrate under conditions effective for forming a barrier coating, for example, by PECVD. Accordingly, the precursor is polymerized, crosslinked, partially or entirely oxidized, or any combination thereof.

[0509] In an additional aspect of either embodiment (i) or embodiment (ii), the coating is a barrier coating, e.g., SiO₂ x It is a coating. Typically, a barrier coating is a barrier to gases or liquids, preferably to water vapor, oxygen, and / or air. The barrier can also be used to establish or maintain a vacuum on the inside of a container coated with the barrier coating, for example, on the inside of a blood collection tube.

[0510] The method of embodiment (i) may include the application of one or more coatings prepared by PECVD from the same or different organosilicon precursors under the same or different reaction conditions. For example, a container is first prepared using hexamethyldisiloxane (HMDSO) as an organosilicon precursor to SiO₂ x It can be coated with a barrier coating.

[0511] The method of embodiment (ii) may involve the application of one or more coatings prepared by PECVD from the same or different silylamine coupling agents under the same or different reaction conditions. For example, a container is first prepared using hexamethyldisiloxane (HMDSO) as a silylamine coupling agent to form SiO₂ x It can be coated with a barrier coating.

[0512] Substrate surface

[0513] For either embodiment (i) or embodiment (ii), the non-specific biomolecular adsorption and / or binding-resistant coating may be applied to a substrate surface, e.g., a container wall, or a part thereof, which may be glass or, e.g., olefin polymer; polypropylene (PP); polyethylene (PE); cyclic olefin copolymer (COC); cyclic olefin polymer (COP); polymethylpentene; polyester; polyethylene terephthalate; polyethylene naphthalate; polybutylene terephthalate (PBT); PVdC (polyvinylidene chloride); polyvinyl chloride (PVC); polycarbonate; polymethyl methacrylate; polylactic acid; polylactic acid; polystyrene; hydrogenated polystyrene; poly(cyclohexylethylene) (PCHE); epoxy resin; nylon; polyurethane polyacrylonitrile; polyacrylonitrile (PAN); ionomer resin; Surlyn® ionomer resin; glass; It is a thermoplastic material that is borosilicate glass or any combination of two or more of these.

[0514] coated containers

[0515] An article coated with a non-specific biomolecule adsorption and / or binding-resistant surface coating according to either embodiment (i) or embodiment (ii) may be a container having a non-specific biomolecule adsorption and / or binding-resistant surface coating on a wall, preferably, an inner wall, e.g., a syringe barrel, or a portion of the container having said coating on a container in contact with a surface, e.g., a syringe plunger or a container cap. The present invention further provides a coating formed from a method as described above, a surface coated with said coating, and a container coated with said coating.

[0516] In the context of either embodiment (i) or embodiment (ii), “container” is an example of a subset of the extensive set of laboratory supplies and medical devices, for instance. The container itself may be any type of article configured to contain or transport a substance. The substance may be a liquid, gas, solid, or any two or more of these. An example of a container is an article having at least one opening and a wall defining an internal contact surface. Optionally, at least a portion of the internal contact surface defines a “contact surface” treated according to the present disclosure. In the context of the present invention, the term “at least” means “equal to or greater than” the integer following such term. Accordingly, in the context of the present invention, the container has one or more openings.

[0517] One or two openings, such as the opening of a sample tube (one opening) or a syringe barrel (two openings), are preferred for either embodiment (i) or embodiment (ii). If the vessel has two or more openings, these may have the same or different sizes. If more than one opening exists, one opening may be used as a gas inlet for the functionalized barrier coating method according to the present invention, and the other opening is capped or left open.

[0518] A container according to either embodiment (i) or embodiment (ii) may be, for example, a sample tube for collecting or storing a biological fluid such as blood or urine; a syringe (or a part thereof, for example, a syringe barrel) for storing or delivering a biologically active compound or composition, for example, a pharmaceutical or pharmaceutical composition; a vial or pipe for storing a biological material or a biologically active compound or composition, for example, a catheter for transporting a biological material or a biologically active compound or composition; or a cuvette for holding a fluid, for example, a biological material or a biologically active compound or composition.

[0519] The container of either embodiment (i) or embodiment (ii) may have any shape. One example of the container has a substantially cylindrical wall adjacent to at least one of its open ends. Generally, the inner wall of this type of container is shaped into a cylindrical shape, for example, in a sample tube or syringe barrel. Sample tubes and syringes or parts thereof (e.g., syringe barrels), vials, and Petri dishes are commercially generally cylindrical, and these are considered.

[0520] Other non-limiting examples of the vessel considered for either embodiment (i) or embodiment (ii) include well or non-well slides or plates, e.g., dropper plates or micro-potency plates. Another non-limiting example of the vessel considered includes pump contact surfaces in contact with the material being pumped, such as impeller contact surfaces, pump chamber contact surfaces, etc. Even other non-limiting examples of the vessel considered include, as various examples, parts of fluid confinement, pumping, processing, filtration, and delivery systems, e.g., intravenous fluid delivery systems, blood processing systems (e.g., cardiopulmonary machines or blood component separators), dialysis systems, or insulin delivery systems. Examples of such parts include piping, pump internal contact surfaces, bags or bottles containing drugs or saline, adapters and tubing connectors for connecting parts of the system together, intravenous needles and needle assemblies, membranes and filters, etc. Other examples of the vessel include measuring and delivery devices, e.g., pipettes, pipette tips, Erlenmeyer flasks, beakers, and graduated cylinders.

[0521] Either embodiment (i) or embodiment (ii) further has an application to any contact surface of a device used or capable of being used to contact a pharmaceutical product or other material within the definition of a "contact surface," such as an ampoule, vial, syringe, bottle, bag, or other containment vessel, stirring rod, impeller, stirring pellet, etc.

[0522] Either embodiment (i) or embodiment (ii) further has an application to any contact surface of a device used or capable of being used to contact a biomolecule or a solution of a biomolecule within the definition of a "contact surface," such as an ampoule, vial, syringe, bottle, bag, or other containment vessel, stirring rod, impeller, stirring pellet, etc.

[0523] Some specific medical devices and laboratory supplies having a fluid or tissue contact surface that can be processed according to either embodiment (i) or embodiment (ii) are as follows: agar petri dishes; blood culture devices; blood sample cassettes; blood sampling systems; bottles; capillary blood collection devices; catheters; cell lifters; cell scrapers; cell sprayers; centrifuge components; collection and transport devices; containers; cover glasses; freeze / freezer boxes; concave microscope slides; direct test and hematology devices; flat microscope slides; microbiology equipment and supplies; microbiology test devices; microscope slides; molecular diagnostic devices; petri dishes; pipettes; pipette tips; sample collection containers; sample collection tubes; sample collection / storage devices; stirring flasks; Erlenmeyer flasks; beakers; graduated cylinders; and syringes.

[0524] Either embodiment (i) or embodiment (ii) provides a vessel treated with the functionalized barrier coating of the present invention, wherein the article comprises, for example, at least one of those described below: a microplate; a centrifuge tube; a pipette tip; a pipette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; a 384-well plate; a 1536-well plate; a round-bottom flask; a beaker; a graduated cylinder; and an Erlenmeyer flask.

[0525] In the context of either embodiment (i) or embodiment (ii), the “container” may be any type of container having at least one opening and a wall defining an inner surface. The substrate may be an inner wall of a container having a lumen. Although the present invention is not necessarily limited to a container of a specific volume, the lumen may have a void volume of, for example, 0.5 to 50 mL, optionally 1 to 10 mL, optionally 0.5 to 5 mL, or optionally 1 to 3 mL. The substrate surface may be part or all of the inner surface of a container having at least one opening and an inner surface.

[0526] Container coating

[0527] When a container is coated by the coating method of either embodiment (i) or embodiment (ii), the coating method comprises several steps. A container having an open end, a closed end, and an inner surface is provided. Surface modification may be performed, for example, on a product, for example, on a polypropylene microplate (NUNC, 96 wells, 0.5 ml, round bottom) having various conditions. For example, this process may include, for example, two stages: i) for example, hydroxylated plastic or SiO x - A substrate conditioning stage for providing a coated glass surface, ii) a copolymerization reagent stage for obtaining a surface coating resistant to non-specific biomolecule adsorption and / or non-specific binding.

[0528] Preferably, either embodiment (i) or embodiment (ii) is performed by placing the open end of the vessel on a vessel holder and establishing a sealed communication between the vessel holder and the interior of the vessel. In this preferred embodiment, gaseous reactants are introduced into the vessel through the vessel holder. In a particularly preferred embodiment, a plasma-enhanced chemical vapor deposition (PECVD) apparatus comprising a vessel holder, an internal electrode, an external electrode, and an output source is used for the coating method according to the present invention.

[0529] A vessel holder of either embodiment (i) or embodiment (ii) has a port for receiving the vessel in a seated position for processing. An internal electrode is positioned to be received within the vessel placed on the vessel holder. An external electrode has an internal portion positioned to receive the vessel placed on the vessel holder. An output source supplies an alternating current to the internal electrode and / or the external electrode to form a plasma within the vessel placed on the vessel holder. Typically, the output source supplies an alternating current to the external electrode, and the internal electrode is grounded. In this embodiment, the vessel defines a plasma reaction chamber.

[0530] In some embodiments of either embodiment (i) or embodiment (ii), the container is impregnated with a copolymer solution prepared as described in US 6828028.

[0531] In either embodiment (i) or embodiment (ii), the substrate may optionally be placed in a reaction chamber, a vacuum is formed over the reaction chamber, and a gas containing oxygen is added to the reaction chamber. Plasma is generated from the gas while optionally heating to form a surface on the prepared substrate.

[0532] In embodiment (i), the prepared surface is subsequently treated with a copolymer solution comprising a solvent and at least one zwitterionic copolymer. In embodiment (ii), the prepared surface is subsequently reacted with a vapor comprising at least one silylamine coupling agent, optionally while heating and optionally in the presence of oxygen, to form an amine functionalized substrate surface. In embodiment (ii), the amine functionalized substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer, optionally in the presence of a polymerization initiator. In either embodiment (i) or embodiment (ii), the optional next step is heating, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0533] Optionally, in embodiment (i), the substrate is placed in a reaction chamber, a vacuum is formed over the reaction chamber, and a gas containing an organosilicon precursor and optionally oxygen is added to the reaction chamber. Plasma is generated from the gas by plasma-enhanced chemical vapor deposition (PECVD) with optional radio frequency irradiation, optional microwave irradiation, and optional heating to form a prepared substrate surface. The prepared surface is then treated with a copolymer solution containing a solvent and at least one zwitterionic copolymer with optional heating, optionally allowed to stand, the copolymer solution is removed, optionally the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface is dried, optionally the substrate surface is heated, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0534] Optionally, in embodiment (ii), SiO x A substrate, which is a coated glass surface, is placed in a reaction chamber, a vacuum is formed over the reaction chamber, and a gas containing oxygen is added to the reaction chamber. Plasma is generated from the gas by plasma-enhanced chemical vapor deposition (PECVD) with optional heating and optionally radio frequency irradiation to form a prepared substrate surface. The prepared surface is then reacted with a vapor containing at least one silyl amine coupling agent in the presence of optional oxygen, with optional heating to form an amine-functionalized substrate surface. The amine functionalized substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer, optionally while heating and optionally in the presence of a polymerization initiator, optionally while standing, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0535] In some embodiments, a substrate is placed in a reaction chamber, a vacuum is formed over the reaction chamber, and in the case of embodiment (i), a gas containing an organosilicon precursor and optionally containing oxygen, or in the case of embodiment (ii), a gas containing oxygen is added to the reaction chamber. In either embodiment (i) or embodiment (ii), plasma is generated from the gas by pulsed plasma-enhanced chemical vapor deposition (PPECVD) with optionally radio frequency irradiation, optionally microwave irradiation, and optionally heating to form a prepared substrate surface. In embodiment (ii), the prepared substrate surface is subsequently reacted with a vapor containing at least one silyl amine coupling agent in the presence of optionally oxygen and optionally heating to form an amine-functionalized substrate surface. The amine functionalized substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer in the presence of a polymerization initiator, optionally while heating, optionally while standing, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0536] Optionally, in embodiment (i) or embodiment (ii), the substrate is placed in a reaction chamber, a vacuum is formed over the reaction chamber, and a gas containing oxygen is added to the reaction chamber. Plasma is generated from the gas by pyrolytic chemical vapor deposition (PCVD) with optionally heating and optionally radio frequency irradiation to form a prepared substrate surface. In embodiment (i), the prepared surface is subsequently treated with a copolymer solution comprising a solvent and at least one zwitterionic copolymer. In embodiment (ii), the prepared substrate surface is subsequently reacted with a vapor containing at least one silylamine coupling agent in the presence of optionally oxygen and optionally heating to form an amine functionalized substrate surface. The amine functionalized substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer, optionally while heating and optionally in the presence of a polymerization initiator, optionally while standing, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface, thereby forming a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0537] Optionally, in embodiment (ii), the substrate is placed in a vacuum plasma reactor, the vacuum plasma reactor is evacuated, and subsequently, a gas containing oxygen, optionally containing argon, and optionally containing nitrogen is added. The gas is subsequently irradiated with RF frequency energy. The irradiation is terminated, and the substrate is exposed to a vapor containing at least one silylamine coupling agent to provide an amine-modified substrate. The amine-modified substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer in the presence of a polymerization initiator, optionally while heating, optionally while standing, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface to thereby form a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0538] Optionally, in embodiment (ii), SiO x - A substrate, which is a coated glass surface, is placed in a vacuum plasma reactor, the vacuum plasma reactor is evacuated, and subsequently, a gas containing oxygen, optionally containing argon, and optionally containing nitrogen is added. The gas is subsequently irradiated with RF frequency energy. The irradiation is terminated, and the substrate is exposed to a vapor containing at least one silylamine coupling agent to provide an amine-modified substrate.

[0539] The amine-modified substrate surface is subsequently treated with a copolymer solution comprising a solvent and at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer in the presence of a polymerization initiator, optionally. In either embodiment (i) or embodiment (ii), the process is continued while optionally heating, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface to thereby form a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface.

[0540] Optionally, in embodiment (i), the substrate is placed in a reaction chamber, a vacuum is formed over the reaction chamber, and a gas containing an organosilicon precursor and optionally containing oxygen is added to the reaction chamber. The prepared surface is then treated with a copolymer solution containing a solvent and at least one zwitterionic copolymer while optionally heating, optionally standing, removing the copolymer solution, optionally drying the non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface, optionally heating the substrate surface to thereby form a non-specific biomolecule adsorption and / or non-specific binding-resistant coated surface. Brief explanation of the drawing

[0541] The technology will be described together with the following drawings, wherein similar reference numerals indicate similar elements: FIG. 1 illustrates a generally described remote conversion plasma processing apparatus useful in a first embodiment, the specific features of which are optional. FIG. 2 illustrates an exemplary plasma reactor configuration for performing remote conversion plasma treatment of a microplate according to a more detailed first embodiment. FIG. 3 is a bar graph illustrating the results of a comparison of biomolecule recovery rates between an unconditioned and unconverted polypropylene microplate, an Eppendorf LoBind® brand microplate, and a microplate treated with an exemplary remote conversion plasma treatment process according to a more detailed first embodiment. FIG. 4 is a bar graph illustrating the results of a comparison of biomolecule recovery rates between a microplate processed by an exemplary remote conversion plasma treatment process according to a more detailed first embodiment and a microplate processed under the same process steps and conditions, except that direct conversion plasma treatment was used instead of remote conversion plasma treatment. FIG. 5 is a bar graph illustrating the results of a comparison of biomolecule recovery rates between a microplate treated with an exemplary remote conversion plasma treatment process according to a more detailed first embodiment and a microplate treated only with a non-polymerizable compound step without a second step. FIG. 6 illustrates an exemplary radio-frequency excited plasma reactor configuration according to FIG. 1 for performing remote conversion plasma treatment of a microplate according to a more detailed first embodiment. FIG. 7 illustrates another exemplary plasma reactor configuration according to FIG. 1 for performing remote conversion plasma treatment of a microplate according to a more detailed first embodiment. FIG. 8 illustrates an exemplary microwave-excited plasma reactor configuration according to FIG. 1 for performing remote conversion plasma treatment of a microplate according to a more detailed first embodiment. FIG. 9 is a plot of the recovery rate of biomolecules (TFN) from an unconditioned and unconverted polypropylene beaker, a treated polypropylene beaker according to a more detailed first embodiment, and a treated polypropylene glass beaker. FIG. 10 illustrates an exemplary reactor configuration for carrying out either a first or second embodiment of the process. Another suitable reactor configuration is the configuration of FIG. 2 as illustrated and described in U.S. Patent No. 7,985,188, incorporated herein by reference. Figure 11 is a plot of protein recovery rate versus protein (BSA) concentration for Example 6. Figure 12 is a plot of protein recovery rate versus protein (PrA) concentration for Example 6. Figure 13 is a plot of protein recovery rate versus protein (PrG) concentration for Example 6. Figure 14 is a plot of protein recovery rate versus protein (BSA) concentration for Example 14. Figure 15 is a plot of protein recovery rate versus protein (PrA) concentration for Example 14. Figure 16 is a plot of protein recovery rate versus protein (PrG) concentration for Example 14. FIG. 17 is a GC-MS (gas chromatography-mass spectroscopy) plot characterizing organic species extracted from a low protein binding treated microplate according to Example 15, showing peak assignments. Figure 18 is a plot similar to Figure 17 for an isopropanol blank according to Example 15. FIG. 19 is a plot similar to FIG. 17 from Example 15 without peak assignment for comparison with FIG. 18. Figure 20 is a comparison of the LC-MS isopropanol extraction ion chromatogram (positive APCI mode) of a low-protein binding treated SiO2 plate (bottom plot) versus an isopropanol blank (top plot) from Example 16. FIG. 21 illustrates the presence of polypropylene components in the unconditioned and unconverted plate extract as a comparison from Example 16 of the LC-MS isopropanol extraction ion chromatogram (positive APCI mode) of the unconditioned and unconverted SiO2 plate (bottom plot) versus the isopropanol blank (top plot). Figure 22 is a comparison of the LC-MS isopropanol extraction ion chromatogram (negative APCI mode) of the low-protein binding treated SiO2 plate (bottom plot) versus the isopropanol blank (top plot) from Example 16. FIG. 23 is an example of a substrate (162) having a contact surface (164) and an internal portion (166), with reference to all embodiments. The following reference numerals are used in this description and the attached drawings: Specific details for implementing the invention

[0542] The present invention will be illustrated in more detail with reference to the following examples, but it should not be understood that the invention is limited thereto.

[0543] Examples

[0544] Example 1 of the first embodiment in more detail

[0545] According to an optional aspect of the first embodiment, a polypropylene 96-well microplate was plasma treated. The process used to treat the microplate utilized a radio-frequency (RF) plasma system. This system was equipped with a gas delivery input, a vacuum pump, and an RF power supply with a matching network. The microplate was oriented toward the opposite side of the plasma and shielded from the plasma along the perimeter of the chamber. These details are illustrated in FIG. 2. The shielding resulted in remote plasma treatment in which the ratio between the radiation density at a remote point on the surface of the microplate and the brightest point of the plasma discharge was less than 0.25.

[0546] The two-stage remote conversion plasma process used according to the present non-limiting embodiment is summarized in Table 2 of the first embodiment in more detail:

[0547]

[0548] The biomolecular binding resistance attributable to this remote conversion plasma process of the first embodiment in more detail on the surface of the treated microplate was analyzed by performing tests of all embodiments. The recovery percentage is the percentage of the original concentration of protein remaining in the solution, that is, not bound to the surface of the microplate.

[0549] In these tests, samples of three different types of microplates were tested for the percentage of recovery. The samples included (1) unconditioned and unconverted polypropylene microplates ("unconditioned and unconverted" samples); (2) polypropylene microplates formed by SiO2 Medical Products and converted according to a first embodiment more detailed as described in Example 1 of this specification ("SiO" samples); and (3) Eppendorf LoBind trademark microplates ("Eppendorf LoBind" samples). The bar chart in FIG. 3 illustrates the results of these comparative tests. As illustrated in FIG. 3 of the first embodiment more detailed, the converted SiO2 plates showed a 60% increase in biomolecule recovery compared to the unconditioned and unconverted samples, and an 8 to 10% increase in biomolecule recovery compared to the Eppendorf LoBind samples.

[0550] Accordingly, remote conversion plasma treatment according to the more detailed first embodiment has been proven to yield a lower biomolecular attachment rate (or, conversely, a higher biomolecular recovery rate) than other known methods. In fact, the comparative data between the SiO2 sample and the Eppendorf LoBind sample is particularly surprising, as the Eppendorf LoBind has been considered the industry standard for protein-resistant laboratory supplies. An 8 to 10% increase in efficacy of the SiO2 plate compared to the Eppendorf LoBind sample represents a significant improvement compared to conventional technology.

[0552] Example 2 of the first embodiment in more detail

[0553] In this embodiment of the first embodiment in more detail, the SiO2 plate of Example 1 was compared with the same microplate converted using the same process steps and conditions as SiO, except that the second sample was treated with direct plasma instead of remote conversion plasma (this is a significant exclusion) ("direct plasma" sample). Surprisingly, as shown in FIG. 4, the direct plasma sample had a biomolecule recovery percentage of 72% after 24 hours, whereas the SiO2 plate (treated under the same conditions / process steps except for the use of remote conversion plasma) had a biomolecule recovery percentage of 90% after 24 hours. This significant change in steps represents an unexpected improvement attributed solely to the use of the remote conversion plasma of the first embodiment in more detail instead of direct plasma.

[0555] Example 3 of the first embodiment in more detail

[0556] In this embodiment of the more detailed first embodiment, the SiO2 sample of Example 1 was compared with the same microplate treated only with the conditioning step (i.e., non-polymerizable compound plasma step or conditioning plasma treatment) of the method of the more detailed first embodiment without the second treatment step (steam plasma step or conversion plasma treatment) ("Step 1 alone" sample). As shown in FIG. 5, the Step 1 alone sample had a biomolecule recovery percentage of 50% after 24 hours at approximately 25°C (aging of all protein samples herein is performed at 25°C unless otherwise indicated), whereas the SiO2 plate (treated under the same conditions / process steps except that it is also converted by remote conversion plasma) had a biomolecule recovery percentage of 90% after 24 hours. Accordingly, using both steps of the method according to the embodiments of the more detailed first embodiment yields a significantly improved biomolecule recovery percentage compared to using only the conditioning step.

[0558] Example 4 (predicted) of the first embodiment in more detail

[0559] An optional advantage considered in addition to the more detailed first embodiment is that it provides a high level of resistance to biomolecular attachment without a compromising high extractability profile. For example, Eppendorf LoBind® laboratory supplies are resistant to biomolecular attachment due to chemical additives that tend to be extracted from the substrate into the solution in contact with the substrate. In contrast, the more detailed first embodiment does not rely on chemical additives mixed into the polymer substrate to provide the substrate with its biomolecular attachment resistance properties. Furthermore, the process according to the more detailed first embodiment does not generate compounds or particles from the treated substrate, nor does it cause compounds or particles to be extracted from the converted substrate in any other way. It was further determined that the pH protection process described herein does not generate compounds or particles from the converted surface, nor does it cause compounds or particles to be extracted from the converted surface in any other way.

[0560] Accordingly, in one optional aspect, the disclosed technology (in the first embodiment described herein in more detail) relates to a method of treating a surface, also referred to as a material or workpiece, to form a converted surface having a biomolecule recovery percentage equal to the biomolecule recovery percentage of the surface prior to the conversion treatment, wherein any conditioning or conversion treatment does not substantially increase the extractable material profile of the description. The applicant anticipates that this will be demonstrated in actual comparative tests between an unconditioned and unconverted surface and a converted surface.

[0562] Example 5 of the first embodiment in more detail

[0563] Tests similar to Example 1 of the first embodiment were performed to compare the biomolecule recovery rates from an unconditioned and unconverted polypropylene (UTPP) laboratory beaker, a remotely converted plasma-treated polypropylene (TPP) laboratory beaker according to the first embodiment, and an unconditioned and unconverted glass laboratory beaker. The biomolecules used were 12 nM dispersions of freeze-dried BSA, FBG, TFN, PrA, and PrG.

[0564] In the first test of the first embodiment in more detail, a biomolecular dispersion was filled into a beaker and mixed by aspirating it several times. The biomolecular recovery rate was measured in relative fluorescence units (RFU). After establishing a 100% recovery baseline by taking an initial RFU reading (0 min), the biomolecular dispersion in the beaker was stirred with a pipette tip for 1 minute and then left on the laboratory bench for the remainder of the test. The biomolecular recovery rate was measured initially, and then samples were taken to measure the percentage of biomolecular recovery at 5-minute intervals. The results are shown in Table 3.

[0565]

[0566] The second test of the first embodiment, the results of which are shown in Table 4, was performed in the same manner as the first test, except that a glass beaker that was not processed according to the first embodiment was used as the substrate.

[0567]

[0568] FIG. 9 of a more detailed first embodiment plots the TFN results of the tables above, showing a plot (34) for an unconditioned and unconverted polypropylene beaker, a plot (36) for a treated polypropylene beaker, and a plot (38) for glass. As shown in FIG. 9, the treated polypropylene beaker provided the highest biomolecule recovery rate after 10 to 30 minutes, the glass provided a lower biomolecule recovery rate after 10 to 30 minutes, and the unconditioned and unconverted polypropylene beaker provided the lowest biomolecule recovery rate at all times after the initial measurement.

[0570] Example 6 of the first embodiment in more detail

[0571] A test similar to Example 1 of the first embodiment was performed to compare the biomolecule recovery rates from two types of multi-well polypropylene plates with respect to protein concentration after 24 hours of contact between the protein and the plate. The "SiO2" plate was formed from polypropylene and plasma-treated according to Example 1. The "CA" (Competitor A) plate was a commercial competitor polypropylene plate provided with a coating to provide reduced non-specific protein binding.

[0572] The results are provided in Table 5 and Figures 11 to 13, which indicate that the recovery rate is independent of concentration, as essentially all proteins of each type were recovered from the converted SiO2 plates at all tested concentrations. In contrast, the protein recovery rate from the CA plates was largely dependent on concentration, particularly at low concentrations.

[0573]

[0575] Example 7 of the first embodiment in more detail

[0576] A test similar to Example 1 of the first embodiment was performed to compare the biomolecule recovery rates from the converted "SiO2" plate and the "CA" plate of the type described in Example 6. The biomolecules used were 1.5 or 3 nM dispersions of freeze-dried BSA, FBG, TFN, PrA, and PrG.

[0577] The conditions and results are shown in Table 6. For BSA, PrA, PrG, and TFN proteins, the converted SiO2 plates provided substantially superior protein recovery rates compared to CA plates. For FBG protein, the converted SiO2 plates provided better protein recovery rates than CA plates.

[0578]

[0580] Example 8 of the first embodiment in more detail

[0581] A test similar to Example 7 of the first embodiment was performed to compare 96-well, 500 µL SiO2 and CA plates. The conditions and results are shown in Table 7. For BSA, PrA, PrG, and TFN proteins, as well as FBG at a concentration of 1.5 nM, the converted SiO2 plates provided substantially superior protein recovery rates compared to the CA plates. FBG at a concentration of 3 nM was abnormal.

[0582]

[0584] Example 9 of the first embodiment in more detail

[0585] A test similar to Example 7 of the first embodiment was performed to compare 96-well, 1000 µL converted SiO2 and CA plates. The conditions and results are shown in Table 8. For BSA, PrA, and PrG proteins, the converted SiO2 plates provided substantially superior protein recovery rates compared to CA plates. FBG protein did not show substantially superior protein recovery rates.

[0586]

[0588] Example 10 of the first embodiment in more detail

[0589] A test similar to Example 7 of the first embodiment was performed to compare 384-well 55 µl (converted SiO2) versus 200 µl (CA) shallow plates. The conditions and results are shown in Table 8. For BSA, PrA, and PrG proteins, the converted SiO2 plates provided substantially superior protein recovery rates compared to the CA plates. FBG protein did not show substantially superior protein recovery rates.

[0590]

[0592] Example 11 of the first embodiment in more detail

[0593] Tests similar to Example 1 of the more detailed first embodiment were performed, and the converted SiO2 plates of the more detailed first embodiment were compared with polypropylene plates treated with StabilBlot® BSA blocker, a commercial treatment agent used to reduce BSA protein attachment sold by SurModics, Inc., Eden Prairie, Minnesota, USA. Conditions and results are shown in Table 10, where the converted SiO2 is the plate according to Example 1, Plate A is a polypropylene plate treated with 5% BSA blocker for 1 hour, and Plate B is a polypropylene plate treated with 1% BSA blocker for 1 hour. Except for FBG protein, the present technology again provided superior results compared to the BSA blocker plates.

[0594]

[0596] Example 12 of the first embodiment in more detail

[0597] A test similar to Example 7 of the first embodiment was performed to compare the protein recovery rates of the converted SiO2 plates according to Example 1 over a long period (1 to 4 months). The conditions and results are shown in Table 11, which exemplify that nearly uniform resistance to protein attachment was observed for all proteins over a significant period.

[0598]

[0600] Example 13 of the first embodiment in more detail

[0601] The binding uniformity between various wells of a single plate was tested using two 96-well plates with deep (500 µL) wells: one was a converted SiO2 plate prepared according to Example 1, except that 2 nM PrA protein was tested in all 96 wells after 2 hours, and the other was a competitor A plate that was retested with 2 nM PrA protein in all 96 wells after 2 hours. After measuring the protein recovery rate from each well on a single plate, the average was calculated, the range was established (determining the highest and lowest recovery rates among the 96 wells), and the standard deviation was calculated. For the converted SiO2 plate, the average recovery rate was 95%, the recovery range was 11%, and the standard deviation was 2%. For the CA plate, the average recovery rate was 64%, the recovery range was 14%, and the standard deviation was 3%.

[0602] The same test as in the previous paragraph was also performed using a 96-well plate with 1000 µL wells. For the converted SiO2 plate, the average recovery rate was 100%, the recovery range was 13%, and the standard deviation was 3%. For the CA plate, the average recovery rate was 62%, the recovery range was 25%, and the standard deviation was 3%.

[0603] This test indicated that the conversion treatment of Example 1 allows for recovery rates between various wells that are at least as uniform as the protein-resistant coating of the CA plate. This suggests that the SiO2 plasma treatment is very uniform across the plate.

[0605] Example 14 of the first embodiment in more detail

[0606] In this example, the protein recovery rates from two types of multi-well polypropylene plates were compared with respect to protein concentration after 96 hours of contact between the protein and the plate. The SiO2 plate was formed from polypropylene and plasma converted according to Example 6. The "EPP" plate was a commercially competitive polypropylene Eppendorf LoBind® plate. The test protocol was identical to that of Example 6, except that the lowest protein concentration (0.1 nM) was much lower than that of Example 6.

[0607] The results are shown in Table 12 and Figures 14 through 16. In fact, the comparative data between the converted SiO2 plates (plots (152, 154, and 158)) and the Eppendorf LoBind® plates (i.e., "EPP" plates, plots (150, 156, and 160)) are particularly surprising, as Eppendorf LoBind® has been considered the industry standard for protein-resistant laboratory supplies. For all three types of proteins tested in this example (i.e., BSA, PrA, and PrG), the protein recovery rate was substantially consistently high for the converted SiO2 plates regardless of concentration. However, for the "EPP" plates, the protein recovery rate decreased dramatically at low concentrations. In particular, at very low concentrations (e.g., between 0.1 nM and less than 1.5 nM), the protein recovery rate for the converted SiO2 plates was significantly better than that for the "EPP" plates.

[0608] For the PrG protein, as indicated by the data marked with an asterisk in Table 12, the 0.1 nM converted SiO2 plate data point was considered anomalous because the actual protein recovery rate of the converted SiO2 plate cannot exceed 100% plus the error limit assigned to that data point. The 0.1 nM EPP plate PrG data point was also considered anomalous because it deviates substantially from the trend of the other data points. These anomalous data points are not shown in Fig. 16.

[0609]

[0611] Example 15 of the first embodiment in more detail

[0612] Characterization of organic species extracted from the low-protein-bound converted microplates using the GC-MS method

[0613] This test was performed on a 96-well microplate to evaluate whether this conversion treatment adds extractable substances to the solution in contact with the substrate. The microplate was formed from polypropylene and converted into plasma according to Example 6.

[0614] Extraction procedure

[0615] 300 µL of isopropanol (IPA) was added to a total of 16 wells in a 96-well microplate. After addition, the plate was tightly covered with a glass plate and stored at room temperature for 72 hours. After extraction, the contents of the 16 wells were combined into a single individual vial, plugged, and inverted to mix. The individual aliquots were transferred to an autosampler vial for GC-MS analysis.

[0616] GC-MS Analysis Conditions and Results

[0617] The GC-MS (gas chromatography-mass spectrometry) analysis conditions are shown in Table 13, the generated plot with eight peak assignments and annotations is shown in Figure 17, and the peak assignments are explained in Table 14.

[0618]

[0619]

[0620] FIGS. 18 and 19 show GC-MS plots measured in the same manner as FIG. 17, characterizing the extracted organic species for an isopropanol blank (Fig. 18) versus the converted low-protein binding treated SiO2 microplate according to Example 15 (Fig. 19).

[0622] Example 16 of the first embodiment in more detail

[0623] Characterization of organic species extracted from low-protein-bound converted SiO2 microplates using the LC-MS method

[0624] Using the LC-MS (liquid chromatography-mass spectroscopy) method, organic extractable substances were analyzed, and whether the conversion treatment added organic extractable substances to the solution in contact with the substrate was evaluated. The extraction procedure was the same as in Example 15.

[0625] LC-MS Analysis Conditions and Results

[0626] Analysis was performed using an Agilent G6530A Q-TOF mass spectrometer, and extracts were run in both positive and negative APCI modes. LC-MS conditions for positive APCI are shown in Table 15, and LC-MS conditions for negative APCI are shown in Table 16.

[0627] Figure 20 shows a comparison of LS-MS isopropanol extraction ion chromatograms (positive APCI mode) of a low-protein-bound converted SiO2 plate (bottom plot) versus an isopropanol blank (top plot).

[0628] Figure 22 is a comparison of LC-MS isopropanol extraction ion chromatograms (negative APCI mode) of a low-protein-bound converted SiO2 plate (bottom plot) ver...

Claims

Claim 1 A method for providing a coated surface resistant to non-specific biomolecule adsorption and / or non-specific biomolecule binding, wherein the method comprises: (a) providing a substrate having a prepared surface; (b) reacting the prepared surface with at least one zwitterionic copolymer to form a coated surface resistant to non-specific biomolecule adsorption and / or non-specific biomolecule binding, wherein the step of reacting the prepared surface with at least one zwitterionic copolymer comprises: reacting the prepared surface with a vapor comprising at least one silylamine coupling agent to provide an amine-modified surface; and contacting the amine-modified surface with a copolymer solution comprising a solvent, wherein the copolymer comprises at least one copolymerizable zwitterionic monomer and at least one copolymerizable epoxy monomer, and optionally performed in the presence of a polymerization initiator. and at least one copolymerizable epoxy monomer is (E)-(oxiran-2-yl)methylbut-2-enoate, (3,3-dimethyloxiran-2-yl)methyl methacrylate, (E)-(oxiran-2-yl)methyl cinnamate, (oxiran-2-yl)methyl 2-methylenebutanoate, 1-(oxiran-2-yl)propyl acrylate, 1-(oxiran-2-yl)ethyl methacrylate, (oxiran-2-yl)methyl 3-methyl-2-methylenebutanoate, (oxiran-2-yl)methyl 2-methylenepentanoate, (3-methyloxiran-2-yl)methyl acrylate, 2-(oxiran-2-yl)propane-2-yl acrylate, (oxiran-2-yl)methyl 2-methylenehexanoate, (3-methyloxiran-2-yl)methyl methacrylate, A method selected from the group consisting of (3,3-dimethyloxiran-2-yl)methyl acrylate and combinations thereof. Claim 2 A method according to claim 1, wherein the step of providing a substrate having a prepared surface comprises: (i) providing the substrate to a reaction chamber; (ii) forming a vacuum in the reaction chamber; (iii) providing a gas containing O₂ or an organosilicon precursor and optionally O₂ near the surface of the substrate; and (iv) generating a plasma from the gas to form the surface of the prepared substrate. Claim 3 In claim 1, at least one silyl amine coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4-aminobutyltriethoxysilane, m-aminophenyltrimethoxysilane, p-aminophenyltrimethoxysilane, o-aminophenyltrimethoxysilane, 3-aminopropyltris(methoxyethoxyethoxy)silane, 11-aminoundecyltriethoxysilane, 3-(m-aminophenoxy)propyltrimethoxysilane, aminopropylsilanetriol, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldiisopropylethoxysilane, 3-aminopropyldimethylethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, N-[3-(trimethoxysilyl)propyl]ethylenediamine, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, N-(6-aminohexyl)aminomethyltriethoxysilane, N-(6-aminohexyl)aminopropyltrimethoxysilane, N-(2-aminoethyl)-11-aminoundecyltrimethoxysilane, (aminoethylaminomethyl)phenethyltrimethoxysilane, N-3-[(amino(polypropyleneoxy)]aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropylsilanetriol, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, N-(2-aminoethyl)-3-aminoisobutylmethyldimethoxysilane, (aminoethylamino)-3-isobutyldimethylmethoxysilane, (3-trimethoxysilylpropyl)diethylenetriamine, N-butylaminopropyltrimethoxysilane, N-ethylaminoisobutyltrimethoxysilane, N-methylaminopropyltrimethoxysilane, N-phenylaminopropyltrimethoxysilane, 3-(N-allylamino)propyltrimethoxysilane, (cyclohexylaminomethyl)triethoxysilane, N-cyclohexylaminopropyltrimethoxysilane, N-ethylaminoisobutylmethyldiethoxysilane, (phenylaminomethyl)methyldimethoxysilane, N-phenylaminomethyltriethoxysilane, N-methylaminopropylmethyldimethoxysilane, bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, 3-(N-styrylmethyl-2-aminoethylamino)-propyltrimethoxysilane hydrochloride, (2-N-benzylaminoethyl)-3-aminopropyl-trimethoxysilane, bis(triethoxysilylpropyl)amine, bis(trimethoxysilylpropyl)amine,Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis[(3-trimethoxysilyl)propyl]-ethylenediamine, Bis(methyldiethoxysilylpropyl)amine, N-allyl-aza-2,2-dimethoxysilacyclopentane, N-aminoethyl-aza-2,2,4-trimethyl-silacyclopentane, N-(3-aminopropyldimethylsila)aza-2,2-dimethyl-2-silacyclopentane, NN-butyl-aza-2,2-dimethoxysilacyclopentane, 2,2-dimethoxy-1,6-diaza-2-silacyclooctane, N-methyl-aza-2,2,4-trimethylsilacyclopentane, A method characterized by being selected from the group consisting of 1-(N-(N',N'-dimethylaminoethyl))-1-aza-2,2,4-trimethyl-2-silacyclopentane and combinations thereof. Claim 4 In claim 1, at least one copolymerizable zwitterionic monomer is 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate; 2-(methacryloxy)ethyl 2-(dimethylammonio)ethyl phosphate; 2-(methacryloxy)ethyl-2-(dimethylammonio)ethyl carboxylate; 2-(methacryloxy)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methiacrylamido)ethyl-2-(dimethylammonio)propylsulfonate; 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate ester; 3-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tripropylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2'-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2'-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3'-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3'-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3'-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3'-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3'-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4'-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4'-(trimethylammonio)butyl phosphate,4-(meth)acryloyloxybutyl-4'-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4'-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4'-(trimethylammonio)butyl phosphate, 2-(vinyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(styryloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(p-vinylbenzyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(acryloylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(vinylcarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonylamino)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(butyroyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, 2-(crotonoyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate, A method characterized by being selected from the group consisting of ethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, butyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, hydroxyethyl-(2'-trimethylammonioethylphosphorylethyl)fumarate, β-carboxyethyl-3,3-dimethylammonium ethyl methacrylate, sulfopropyl-3,3-dimethylammonium ethyl methacrylate, and combinations thereof. Claim 5 A method according to claim 1, characterized in that the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, dimethyl sulfoxide, methylene chloride, 1,2-dichloroethane, and combinations thereof. Claim 6 A method according to claim 1, characterized in that the material is a polymer. Claim 7 The method according to claim 6, wherein the polymer is selected from the group consisting of olefin polymers; polypropylene (PP); polyethylene (PE); cyclic olefin copolymer (COC); cyclic olefin polymer (COP); polymethylpentene; polyester; polyethylene terephthalate; polyethylene naphthalate; polybutylene terephthalate (PBT); PVdC (polyvinylidene chloride); polyvinyl chloride (PVC); polycarbonate; polymethyl methacrylate; polylactic acid; polystyrene; hydrogenated polystyrene; poly(cyclohexylethylene) (PCHE); epoxy resin; nylon; polyurethane polyacrylonitrile; polyacrylonitrile (PAN); and ionomer resin. Claim 8 A method according to claim 1, characterized in that the non-specific biomolecule adsorption and / or non-specific biomolecule binding resistant coated surface has reduced biomolecule binding compared to an untreated substrate. Claim 9 A method according to claim 8, wherein the biomolecule is selected from the group consisting of nucleotides, amino acids, sugars, fatty acids, nucleic acid molecules, polypeptides, polynucleotides, polysaccharides, lipids, steroids, glycoproteins, lipoproteins, glycolipids, DNA, DNA-protein conjugates, RNA, RNA-conjugates, antibodies, and receptors, receptor fusion constructs, receptor fusion proteins, chimeric proteins, antibody fusion constructs, and antibody fusion proteins. Claim 10 A method according to claim 1, characterized in that the material is the surface of the container. Claim 11 The method according to claim 10, characterized in that the vessel is selected from the group consisting of a microplate; a centrifuge tube; a pipette tip; a cuvette, a microwell plate; an ELISA plate; a microtiter plate; a 96-well plate; a 384-well plate; a 1536-well plate; a round-bottom flask; and an Erlenmeyer flask. Claim 12 A method characterized in that, in paragraph 10, the material is the inner surface of the container. Claim 13 A method according to claim 12, characterized in that the container is a vial, syringe, or cartridge. Claim 14 The method according to claim 13, wherein the inner surface comprises a coating or layer of PECVD-deposited SiOxCyHz or SiNxCyHz, wherein x is 0.5 to 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is 0.6 to 3 as measured by XPS, and z is 2 to 9 as measured by Rutherford backscatter spectroscopy (RBS). Claim 15 A method according to claim 13, wherein the inner surface comprises a barrier coating or layer of SiOx, wherein x is 1.5 to 2.9 as measured by X-ray photoelectron spectroscopy (XPS). Claim 16 A product comprising a surface coated with resistance to non-specific biomolecule adsorption and / or non-specific biomolecule binding, manufactured by the method according to claim 1. Claim 17 In paragraph 16, the product is a container, and is characterized in that at least a portion of the inner surface of the container comprises a surface coated to resist non-specific biomolecule adsorption and / or non-specific biomolecule binding.

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