Methods for detecting brush polymer macromolecules and biomolecules

Abstract

Macromolecular structures including surfaces, anchoring sites, and macromolecular chains, their compositions, and methods for producing them are provided herein. Systems and kits containing macromolecular structures are also provided herein. The analysis and separation of biomolecules typically require cumbersome methods and rely on fine-tuning of analytical parameters. Often, the methods require inducing polymerization, which may not be feasible for all proteins and ligands and is irreversible.

Description

[Technical Field]

[0001] cross reference This application claims the benefits of U.S. Provisional Application No. 63 / 517,515, filed on 3 August 2023, which is incorporated herein by reference in its entirety. [Background technology]

[0002] background The analysis and separation of biomolecules typically require cumbersome methods and rely on fine-tuning of analytical parameters. Often, the methods require inducing polymerization, which may not be feasible for all proteins and ligands and is irreversible. There is a need for improved systems for the separation and subsequent analysis of biomolecules. This disclosure provides macromolecular structures, as well as their compositions, methods, and systems, to address this need. [Overview of the project] [Means for solving the problem]

[0003] Abstract It is a macromolecular structure, (I) surface; (II) Mooring portions coupled to the surface; and (III) Macromolecule chain It contains, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain, [ka] [ka] [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH; Q is -CH2- or ethylene glycol; A is structure: [Chemistry] It is a polymer side chain containing repeating units derived from monomers represented by; m is an integer selected from 1 to 20; [Chemistry] is a single bond or a double bond; R 1 、R 2 、R 1’ 、R 2’ 、and R 3’ each is independently selected from hydrogen or -C1-C6 alkyl; R 3 is hydrogen, C1-C6 alkyl, or a 3-, 5-, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyls; R 4 is absent, hydrogen, sulfonate, carboxylate, C1-C4 alkylene, amine, quaternary ammonium cation, or C1-C6 alkyl optionally substituted with halogen; R 5 is hydrogen, C1-C6 alkyl, C1-C8 alkyl substituted with one or more hydroxyls, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, a 3-, 5-, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyls or oxo, or C1-C n1 ethylene glycol, amine, hydroxyl, aryl, or C1-C8 alkylamine further optionally substituted with sulfonate, C1-C8 alkoxy optionally substituted with one or more oxo or halogen, one or more pyrenes, two or more fused 5-6 membered rings optionally further substituted, benzyl optionally substituted, trimethoxysilane, or -C1-C3 alkyl optionally substituted with phosphocholine, C1-C 12 alkylamine, or C1-C4 alkylene(alkylyne); R 6is hydrogen or a C1-C6 alkyl group. R 7 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines optionally further substituted with ethylene glycol, amines, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes; two or more condensed 5-6 membered rings optionally further substituted; -C1-C3 alkyls optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; or C1-C4 alkylenes. R 8 These are C1-C6 alkyl groups, divalent metals, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1 [This is an integer selected from 1 to 100.] Macromolecular structures comprising two or more distinct repeating units derived from monomers represented by structures selected from the group consisting of R 3 Large molecular structures in which R is methyl are further provided herein. 5 C1~C n1 A macromolecular structure of ethylene glycol is further provided herein.

[0004] It is a macromolecular structure, (I) surface; (II) Mooring portions coupled to the surface; and (III) Macromolecule chain It contains, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain, [ka] [ka] [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH; Q is -CH2- or ethylene glycol; A is structure: [ka] A polymer side chain containing repeating units derived from a monomer represented by; m is between 1 and 6; R 1 , R 2 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups; R 4 These are C1-C6 alkyl, C1-C4 alkylene, C1-C6 alkyl, sulfonate, amine, quaternary ammonium cation, or carboxylate, which are absent, substituted as needed with hydrogen, or halogens; R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1C1-C8 alkylamines further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally substituted (e.g., two or more fused 6-membered rings optionally substituted); two or more fused 5-6 membered rings optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; C1-C3 alkyls optionally substituted with phosphorocholine. 12 Alkylamines, or C1-C4 alkylenes; R 6 These are hydrogen or linear C1-C6 alkyl groups. R 7 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines further substituted with ethylene glycol, amines or sulfonates, C1-C8 alkoxys optionally substituted with one or more oxo or halogens, one or more pyrenes, two or more condensed 5- or 6-membered rings optionally further substituted (e.g., two or more condensed 6-membered rings optionally further substituted), optionally substituted benzyl, trimethoxysilane, or phosphorocholine-substituted -C1-C3 alkyls, or C1-C4 alkylenes; R 8 These are C1-C6 alkyl groups, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1 is an integer selected from 1 to 100; However, R 3 If it is CH3, then R 4 is CH3, or R 5If C1-C8 alkyl is substituted with hydroxyl, then C1-C8 is further substituted. Macromolecular structures comprising repeating units derived from monomers represented by structures selected from the group consisting of are provided herein.

[0005] A macromolecular structure comprising (I) a surface and (II) macromolecular chains coupled to the surface, wherein the macromolecular chains comprise repeating units of formula (I), is provided herein: [ka] [In the formula, R 1’’ , R 2’’ , and R 3’’ Each of them is independently either hydrogen or a C1-C6 alkyl group; L is the linker part; A is [ka] [ka] A polymer side chain containing repeating units derived from monomers represented by a structure selected from the group consisting of the following: Each of X and Y is independently -C-, -O-, or -N-; Z is -O- or -NH; R 1 , R 2 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups; R 4These are C1-C6 alkyl groups that are absent, hydrogen, sulfonates, carboxylates, C1-C4 alkylenes, amines, quaternary ammonium cations, or C1-C6 alkyl groups substituted as needed with halogens; R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally substituted (e.g., two or more fused 6-membered rings optionally substituted); two or more fused 5-6 membered rings optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; C1-C3 alkyls optionally substituted with phosphorocholine. 12 Alkylamines, or C1-C4 alkylenes; R 6 These are hydrogen or linear C1-C6 alkyl groups. R 7 These are hydrogen, C1-C6 alkyl, a 3, 5, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyl or oxo, a substituted benzene, a hydroxyl-substituted C1-C6 alkyl, or an optionally substituted C1-C8 alkyl sulfonate; R 8 These are C1-C6 alkyl groups, divalent metals, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1 is an integer selected from 1 to 100; n is an integer selected from 1 to 10,000. Large molecular chains, structure: [ka] Macromolecular structures comprising repeating units derived from monomers represented by are further provided herein. Macromolecular structures comprising macromolecular chains comprising repeating units derived from monomers represented by the structures in Table 1 are further provided herein. Macromolecular structures comprising macromolecular chains comprising repeating units derived from monomers represented by the structures in Table 2 are further provided herein. Macromolecular structures, [ka] [ka] Macromolecular structures having the structure represented by are further provided herein.

[0006] A method for producing a macromolecular structure as described herein is provided herein, comprising the steps of: providing a surface; coupling a polymer initiator to the surface to form an initiator surface; and contacting the initiator surface with a monomer as described herein to form a macromolecular structure. A method is further provided herein in which the surface comprises particles. A method is further provided herein in which the particles comprises a diameter of about 100 nm to about 500 nm.

[0007] A method for producing a macromolecular structure is provided herein, comprising the steps of: providing a surface; coupling vinyl groups to the surface to form a vinyl-functionalized surface; contacting the vinyl-functionalized surface with a crosslinked monomer and a monomer selected from hydroxyalkyl methacrylate, aminoalkyl methacrylate, alkynyl methacrylate, glycidylalkyl methacrylate, hydroxyalkyl acrylate, aminoalkyl acrylate, alkynyl acrylate, or glycidylalkyl acrylate to form a crosslinked polymer coupled to the surface; coupling a polymer initiator to the crosslinked polymer to form an initiator surface; and contacting the initiator surface with the monomers described herein to form a macromolecular structure. [ka] [In the formula, X is a halogen; R 10 A method is further provided herein, represented by [an initiator group].

[0008] This specification provides macromolecular structures as described herein, and compositions comprising biomolecules adsorbed to macromolecular structures. Further provided herein are compositions in which at least 100 different biomolecules are adsorbed to the macromolecular structures.

[0009] A method for identifying proteins in a sample is provided herein, the method comprising the steps of: incubating one or more macromolecular structures described herein with a biological sample containing biomolecules to form a biomolecular corona; isolating at least a portion of the biomolecules in the biomolecular corona; and assaying the biomolecular corona. A method is further provided herein in which the assaying step can identify a group of 1 to 20,000 proteins.

[0010] A kit for identifying molecules in a biological sample is provided herein, wherein the kit comprises one or more macromolecular structures provided herein.

[0011] A system for identifying biomolecules in a biological sample is described herein, the system being an automated system programmed to perform a series of steps, the system comprising: a macromolecular structure provided herein; a suspension solution; a biological sample containing a certain concentration of protein; and a network of units having distinct functions for isolating biomolecules adsorbed to the macromolecular structure.

[0012] Novel features of this disclosure are described in detail in the appended claims. A better understanding of the features and advantages of this disclosure is obtained by referring to the following detailed description illustrating exemplary embodiments in which the principles of this disclosure are utilized, and the accompanying drawings (hereinafter also referred to as “Drawings” and “Figures”) are as follows. [Brief explanation of the drawing]

[0013] [Figure 1] Figure 1 shows an exemplary synthetic scheme for the preparation of the macromolecular structures described herein by contacting monomers with an initiator surface.

[0014] [Figure 2] Figure 2 shows an exemplary synthetic scheme for preparing the macromolecular structures described herein by contacting a vinyl-functionalized surface with a crosslinked monomer and a second monomer.

[0015] [Figure 3A] Figure 3A shows a scanning electron microscope image of the macromolecular structure described herein. Figure 3B shows a transmission electron microscope image of the macromolecular structure described herein. [Figure 3B] Figure 3A shows a scanning electron microscope image of the macromolecular structure described herein. Figure 3B shows a transmission electron microscope image of the macromolecular structure described herein.

[0016] [Figure 4] Figure 4 shows the synthetic scheme for the preparation of Compound 1.

[0017] [Figure 5] Figure 5 shows the synthetic scheme for the preparation of Compound 2.

[0018] [Figure 6] Figure 6 shows the synthetic scheme for the preparation of Compound 3.

[0019] [Figure 7] Figure 7 shows the synthetic scheme for the preparation of the block copolymer.

[0020] [Figure 8] Figure 8 shows the synthetic scheme for the preparation of a macromolecular chain containing various monomers.

Mode for Carrying Out the Invention

[0021] Detailed Description Specific Definitions Where used herein and in the appended claims, the singular forms “a,” “an,” and “the” include multiple references unless the context explicitly indicates otherwise. Thus, for example, a reference to “one drug” includes multiple such drugs, and a reference to “the cell” includes one or more cells (or more cells) and references to their equivalents known to those skilled in the art. Where a range is used herein for physical properties such as molecular weight or chemical properties such as chemical formula, it is intended to include all combinations and partial combinations of the range, as well as the specific embodiments contained therein. The term “about” means, where it refers to a number or range of numbers, that the number or range being referenced is an approximation within experimental variation (or statistical experimental error), and therefore the number or range being stated may vary by 1% to 15%. The term “comprising” (and related terms such as “comprise” or “comprises” or “having” or “including”) is not intended to exclude other specific embodiments, such as substances, compositions, methods, or processes of any composition described herein, which may also “consist of” or “essentially consist of” the described properties.

[0022] "Amino" refers to the -NH2 radical.

[0023] "Cyano" refers to the -CN radical.

[0024] "Nitro" refers to the -NO2 radical.

[0025] "Oxo" refers to the =O radical.

[0026] "Hydroxyl" refers to the -OH radical.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art in which this disclosure pertains. All patents and publications referenced herein are incorporated herein by reference.

[0028] "Alkyl" refers to a linear or branched saturated hydrocarbon monoradical, optionally substituted, preferably having 1 to 15 carbon atoms (i.e., C1 to C15). 15 Alkyl). In certain embodiments, alkyl contains 1 to 13 carbon atoms (i.e., C1 to C13). 13 Alkyl). In certain embodiments, the alkyl contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). Whenever it appears herein, a numerical range such as "C1-C3 alkyl" means that the alkyl consists of 1 carbon atom, 2 carbon atoms, or 3 carbon atoms. In other embodiments, the alkyl contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl contains 5 to 15 carbon atoms (i.e., C5-C 15Alkyl). In other embodiments, the alkyl group contains 5 to 8 carbon atoms (i.e., C5 to C8 alkyl). In other embodiments, the alkyl group contains 2 to 5 carbon atoms (i.e., C2 to C5 alkyl). In other embodiments, the alkyl group contains 3 to 5 carbon atoms (i.e., C3 to C5 alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). In other embodiments, examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, as well as longer alkyl groups, such as heptyl and octyl. The alkyl group is bonded to the remainder of the molecule by a single bond. Unless otherwise specifically stated herein, alkyl groups may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, sulfone, mercapto, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkyl groups may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, -NO2, or -C≡CH. In some embodiments, alkyl groups may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, alkyl groups may be optionally substituted with halogens, for example, F. In some embodiments, alkyl groups are unsubstituted.

[0029] When used in this specification, C1 to C x (or C 1~x ) is C1~C2, C1~C3...C1~C x This includes. Simply as an example, a group designated as "C1-C4" indicates that there are 1 to 4 carbon atoms in its part, i.e., a group containing 1 carbon atom, 2 carbon atoms, 3 carbon atoms, or 4 carbon atoms. Therefore, simply as an example, "C1-C4 alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl group, i.e., the alkyl group is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Also, as an example, C0-C2 alkylenes include direct bonds, -CH2-, and -CH2CH2- links.

[0030] "Alkoxy" refers to a radical bonded through the oxygen atom of the formula -O-alkyl, where alkyl is the alkyl chain as defined above. Unless otherwise specifically stated herein, the alkoxy group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkoxy is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen. In some embodiments, the alkoxy is unsubstituted.

[0031] "Alkenyl" refers to a linear or branched hydrocarbon chain radical group that contains at least one carbon-carbon double bond and is optionally substituted, preferably having 2 to 12 carbon atoms (i.e., C2 to C2). 12Alkenyls. In certain embodiments, the alkenyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkenyls). In certain embodiments, the alkenyl contains 4 to 8 carbon atoms (i.e., C4-C6 alkenyls). In other embodiments, the alkenyl contains 6 to 8 carbon atoms (i.e., C6-C8 alkenyls). In certain embodiments, the alkenyl contains at least one double bond at the end of the carbon chain. In other embodiments, the alkenyl contains at least one double bond in the middle of the carbon chain. It should be understood that the group can be in either a cis or trans configuration with respect to the double bond, and that both isomers are included. Examples, but are not limited to, ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl, etc. Whenever it appears herein, a numerical range such as “C2-C6 alkenyl” means that the alkenyl group may consist of two carbon atoms, three carbon atoms, four carbon atoms, five carbon atoms, or six carbon atoms. Unless otherwise specifically stated herein, the alkenyl group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkenyl may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkenyl may be optionally substituted with halogen. The alkenyl group is attached to the remainder of the molecule by a single bond, such as ethenyl (i.e., vinyl), propa-1-enyl (i.e., allyl), buta-1-enyl, penta-1-enyl, penta-1,4-dienyl, etc. Unless otherwise specifically stated herein, the alkenyl group may be substituted as needed with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc.In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen. In some embodiments, the alkenyl is unsubstituted.

[0032] "Alkynyl" refers to a linear or branched hydrocarbon chain radical group that contains at least one carbon-carbon triple bond and is optionally substituted, preferably having 2 to 12 carbon atoms (i.e., C2 to C2). 12 Alkynnyl). In certain embodiments, the alkynyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, the alkynyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, the alkynyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkynyl). Whenever it appears herein, numerical ranges such as "C2-C6 alkynyl" mean that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms. The alkynyl is bonded to the remainder of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, 2-propynyl, 2-butynyl, 1,3-butadiinyl, etc. Unless otherwise specifically stated herein, the alkynyl group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkynyl may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl may be optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkynyl may be optionally substituted with halogen. In some embodiments, the alkynyl is unsubstituted.

[0033] An "alkylene" or "alkylene chain" refers to a optionally substituted linear or branched divalent hydrocarbon chain having 1 to 12 carbon atoms, preferably having methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is bonded to the rest of the molecule through single bonds and to the radical group through single bonds. The bonding sites of the alkylene chain to the rest of the molecule and the radical group may be through any two carbon atoms in the chain. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C1-C8 alkylene). In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene). Unless otherwise specifically stated herein, the alkylene group may be substituted as needed with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkylene is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, alkylene is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, alkylene is optionally substituted with halogen.In some embodiments, the alkylene is -CH2-, -CH2CH2-, or -CH2CH2CH2-. In some embodiments, the alkylene is -CH2-. In some embodiments, the alkylene is -CH2CH2-. In some embodiments, the alkylene is -CH2CH2CH2-. In some embodiments, the alkylene is unsubstituted.

[0034] "Aryl" refers to a radical derived from a hydrocarbon ring system containing at least one aromatic ring. In some embodiments, the aryl contains hydrogen and 5 to 30 carbon atoms. The aryl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include condensed (when condensed with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through the atoms of the aromatic ring) or bridging ring systems. In some embodiments, the aryl is a 6 to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl. Examples of aryl radicals, but not limited to, derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluorantene, fluorene, indan, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. In some embodiments, the aryl is phenyl. Unless otherwise specifically stated herein, aryls may be optionally substituted with, for example, halogens, aminos, alkylaminos, aminoalkyls, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, heteroalkyls, alkoxys, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, -S(O)2NH-C1~C6 alkyls, etc. In some embodiments, aryls may be optionally substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, -OMe, -NH2, -NO2, -S(O)2NH2, -S(O)2NHCH3, -S(O)2NHCH2CH3, -S(O)2NHCH(CH3)2, -S(O)2N(CH3)2, or -S(O)2NHC(CH3)3. In some embodiments, aryls may be optionally substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, or -OMe. In some embodiments, aryls may be optionally substituted with halogens.In some embodiments, the aryl is substituted with an alkyl, alkenyl, alkynyl, haloalkyl, or heteroalkyl group, and each alkyl, alkenyl, alkynyl, haloalkyl, or heteroalkyl group is independently either unsubstituted or substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2 group. In some embodiments, the aryl is unsubstituted.

[0035] "Aralkyr" is formula -R c - Refers to the aryl radical, in the formula, R c These are alkylene chains as defined above, such as methylene and ethylene.

[0036] "Aralkenyl" is expressed by formula -R d - Refers to the aryl radical, in the formula, R d This is the alkenylene chain defined above. "Aralkynyl" is defined by formula -R e - Refers to the aryl radical, in the formula, R e This is the alkynylene chain as defined above.

[0037] "Carbon ring" refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. The carbon ring may include 3- to 10-member monocyclic rings and 6- to 12-member bicyclic rings (such as spiro, fused, or bridged rings). Each ring of the bicyclic carbon ring may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, for example, phenyl, may be fused with a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of the carbon ring when the valency permits. In an exemplary embodiment, an aromatic ring, for example, phenyl, may be fused with a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. The bicyclic carbon ring includes any combination of saturated, unsaturated, and aromatic bicyclic rings when the valency permits. The bicyclic carbon ring includes any combination of ring sizes, such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-5 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Exemplary carbon rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The term "unsaturated carbon ring" refers to a carbon ring having at least one degree of unsaturation, excluding aromatic carbon rings. Examples of unsaturated carbon rings include cyclohexadiene, cyclohexene, and cyclopentene. The term "saturated cycloalkyl" as used herein refers to a saturated carbon ring. Exemplary carbon rings include cyclopropyl, cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, norbornyl, and naphthyl. The carbon ring may be optionally substituted by one or more substituents, such as the substituents described herein.

[0038] "Cycloalkyl" refers to a stable, partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or heteroaryl ring, cycloalkyl is bonded through a non-aromatic ring atom), bridged, or spiro ring systems. Representative cycloalkyls include, but are not limited to, 3 to 15 carbon atoms (C3-C15 Cycloalkyl), 3 to 10 carbon atoms (C3 to C 10 Examples of monocyclic cycloalkyls include cycloalkyls having 3 to 8 carbon atoms (C3-C8 cycloalkyls), 3 to 6 carbon atoms (C3-C6 cycloalkyls), 3 to 5 carbon atoms (C3-C5 cycloalkyls), or 3 to 4 carbon atoms (C3-C4 cycloalkyls). In some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl or carbocyclic compounds include adamantyl, norbornyl, dekalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane and bicyclo[3.3.2]decane, as well as 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Examples of partially saturated cycloalkyl compounds include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise specifically stated herein, cycloalkyl compounds may be substituted as needed with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the cycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the cycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl group is optionally substituted with halogen. In some embodiments, the cycloalkyl group is unsubstituted.

[0039] "Cycloalkylalkyl" is defined by formula -Rc - Refers to a cycloalkyl radical, where R is in the formula. c This is the alkylene chain described above.

[0040] "Cycloalkylalkoxy" is a compound of the formula -OR c - Refers to a radical bonded through the oxygen atom of a cycloalkyl group, where R is in the formula. c This is the alkylene chain described above.

[0041] "Halo" or "halogen" refers to halogen substituents, such as bromo, chloro, fluoro, and iodo substituents.

[0042] As used herein, the terms “haloalkyl” or “haloalkane” refer to the alkyl radicals defined above, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc., which are substituted with one or more halogen radicals. In some embodiments, the alkyl portion of the fluoroalkyl radical may be further substituted as needed. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, as well as any other suitable combination of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). If an alkyl group is substituted with one or more halogen radicals, each halogen can be independently selected, for example, 1-chloro,2-fluoroethane.

[0043] "Fluoroalkyl" refers to the alkyl radicals defined above, which are substituted by one or more fluororadicals, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc.

[0044] "Hydroxyalkyl" refers to the alkyl radical as defined above, which is substituted with one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Examples of hydroxyalkyls include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0045] "Aminoalkyl" refers to the alkyl radical as defined above, which is substituted with one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Examples of aminoalkyls include aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0046] "Disulfide" refers to two sulfur atoms bonded together, where each sulfur atom optionally contains a substituted alkyl chain. In some embodiments, the disulfide may be RSS-R'. In some embodiments, R and R' may be the same. In some embodiments, R and R' may be different. Each R and R' is independently C1-C 12 Alkyls may be selected. In certain embodiments, R or R' may be substituted with an amine, sulfone, or carboxylic acid.

[0047] The term "heteroalkyl" refers to an alkyl group in which one or more of the alkyl backbone atoms are selected from atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof. In a heteroalkyl group, the carbon atoms of the heteroalkyl group are bonded to the remainder of the molecule. In one embodiment, the heteroalkyl group is a C1-C6 heteroalkyl group, where the heteroalkyl group consists of 1-6 carbon atoms and one or more atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof, and the carbon atoms of the heteroalkyl group are bonded to the remainder of the molecule. Examples of such heteroalkyl groups are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, or -CH(CH3)OCH3. Unless otherwise specifically stated herein, heteroalkyls are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyls are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroalkyls are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroalkyls are optionally substituted with halogens. In some embodiments, heteroalkyls are unsubstituted.

[0048] "Hypercycloalkyl" refers to a stable 3-24 membered partial or fully saturated ring radical containing 2-23 carbon atoms and at least one ring heteroatom. In some embodiments, the heterocycloalkyl contains 1-8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur. Unless otherwise specifically stated herein, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include condensed (when condensed with an aryl or heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom) or bridging ring systems, and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be oxidized as necessary, and the nitrogen atom may be quaternized as necessary.

[0049] Typical heterocycloalkyls are not limited to those with 2 to 15 carbon atoms (C2-C2). 15 Heterocycloalkyl), 2 to 10 carbon atoms (C2 to C 10Examples include heterocycloalkyls having 2 to 8 carbon atoms (C2-C8 heterocycloalkyls), 2 to 6 carbon atoms (C2-C6 heterocycloalkyls), 2 to 5 carbon atoms (C2-C5 heterocycloalkyls), or 2 to 4 carbon atoms (C2-C4 heterocycloalkyls). In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. Examples of such heterocycloalkyl radicals include, but are not limited to, azilidinyl, azetidinyl, dioxolanil, thienyl[1,3]dithianil, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, and 4-piperazinyl. Examples include lidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianil, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes, but is not limited to, all ring forms of carbohydrates, including monosaccharides, disaccharides, and oligosaccharides. When referring to the number of carbon atoms in a heterocycloalkyl, it should be understood that the number of carbon atoms in a heterocycloalkyl is not the same as the total number of atoms constituting the heterocycloalkyl (including heteroatoms) (i.e., the skeletal atoms of the heterocycloalkyl ring). Unless otherwise specifically stated herein, heterocycloalkyls may be substituted as needed with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc.In some embodiments, the heterocycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl group is optionally substituted with halogen. In some embodiments, the heterocycloalkyl group is unsubstituted.

[0050] A “heterocyclic” refers to a saturated, unsaturated, or aromatic ring containing one or more ring heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocyclics include, for example, 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings (such as spirocyclic, condensed, or bridging rings). Unless otherwise specifically stated herein, heterocyclic radicals are monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, which may include condensed, bridging, or spirocyclic ring systems as they may be. Heteroatoms in heterocyclic radicals are oxidized as they may be. One or more nitrogen atoms, if present, are quaternized as they may be. Heterocyclic radicals may be partially or fully saturated. Heterocyclines are bonded to the remainder of the molecule through any atom of the ring. Examples of such heterocyclyl radicals include, but are not limited to, dioxolanil, thienyl[1,3]dithianil, decahydroisoquinolyl, imidazolinil, imidazolidinil, isothiazolidinil, isoxazolidinil, morpholinil, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinil, 2-oxopiperidinil, 2-oxopyrrolidinil, oxazolidinil, piperidinil, piperazinil, 4-piperidonil, pyrrolidinil, pyrazolidinil, quinuclidinil, thiazolidinil, tetrahydrofuryl, trithianil, tetrahydropyranil, thiomorpholinil, thiamorpholinil, 1-oxo-thiomorpholinil, and 1,1-dioxo-thiomorpholinil. Unless otherwise specifically stated herein, the term “heterocyclyl” means including the heterocyclyl radical as defined above, which is optionally substituted by one or more substituents.For example, the heterocyclyl is alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R. b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -CN, -R b -O-R e -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a)2 (wherein t is 1 or 2) may optionally be substituted by one or more substituents selected from the formula, where each R a R is independently hydrogen, alkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (as may be substituted as necessary with halogen, hydroxy, methoxy, or trifluoromethyl), and each R b R is an independent, directly bonded, or linear or branched alkylene or alkenylene chain. e These are linear or branched alkylene or alkenylene chains, and each of the above substituents is unsubstituted unless otherwise indicated.

[0051] A "heteroaryl" or "aromatic heterocyclic" refers to a cyclic radical comprising a carbon atom and one or more ring heteroatoms (e.g., selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur), as well as at least one aromatic ring. In some embodiments, a heteroaryl is a 5-14 membered cyclic radical comprising 1-13 carbon atoms and 1-6 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur. A heteroaryl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic cyclic system, which may include condensed (when condensed with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through aromatic ring atoms) or bridging cyclic systems, and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be oxidized as necessary, and the nitrogen atom may be quaternized as necessary. In some embodiments, the heteroaryl is a 5-10 membered heteroaryl. In some embodiments, the heteroaryl is a 5-6 membered heteroaryl.Examples, though not limited to them, include: azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxolyl, benzofuranil, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanil, benzonaphthofuranil, benzoxazolyl, benzodioxolyl, benzodioxynil, benzopyranil, benzopyranonil, benzofuranil, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, sinnolinil, dibenzofuranil, dibenzothiophenyl, furanil, furanonil, isothiazolyl, imidazolyl, indazolyl, indolyl, indazoli Examples include isoindolyl, indolinyl, isoindolyl, isoquinolyl, indolidinyl, isoxazolyl, naphthilidinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxyranil, 1-oxidepyridinyl, 1-oxidepyrimidinyl, 1-oxidepyradinyl, 1-oxidepyradinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxadinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyridinyl, pyrimidinyl, pyridadinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise specifically stated herein, heteroaryls may be optionally substituted with, for example, halogens, aminos, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, alkoxys, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, etc. In some embodiments, heteroaryls may be optionally substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroaryls may be optionally substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, or -OMe.In some embodiments, the heteroaryl is substituted with a halogen as needed. In some embodiments, the heteroaryl is unsubstituted.

[0052] The term “substituted” refers to a moiety having a substituent that replaces one or more carbons or substituteable heteroatoms of a structure, for example, a hydrogen on an NH group. It will be understood that “substituted” or “substituted with” implies that such substitutions follow an acceptable valency of the substituted atom and substituent, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformations such as rearrangement, cyclization, or elimination. In certain embodiments, “substituted” refers to a moiety having a substituent that replaces two hydrogen atoms on the same carbon atom, for example, two hydrogen atoms on a single carbon atom with an oxo, imino, or thioxo group. As used herein, the term “substituted” is intended to include all acceptable substituents of an organic compound. In a broad range of embodiments, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. There may be one or more acceptable substituents, and they may be the same or different for a given organic compound. For the purposes of this disclosure, the heteroatom, for example, nitrogen, may have any acceptable substituents of the organic compound described herein that satisfy the hydrogen substituent and / or the valence of the heteroatom.

[0053] In some embodiments, the substituent is any substituent described herein, such as halogen, hydroxyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), -R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a ,-R b -OC(O)-N(R a )2, -R b -N(Ra )2, -R b -C(O)R a ,-R b -C(O)OR a ,-R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t Ure a (wherein the formula t is 1 or 2), and -R b -S(O) t N(R a )2 (wherein t is 1 or 2); and may also include alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralquinyl, cycloalkyl, cycloalkylalkyl, and heterocycles, any of which are alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), SF 5 ,-R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a ,-R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a,-R b -C(O)OR a ,-R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t Ure a (wherein the formula t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2) can be substituted as needed by each R in the formula. a The elements are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, and heterocycle, and each R a If the valency is acceptable, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), -R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a ,-R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a ,-R b -C(O)ORa ,-R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t R a (In the formula, t is either 1 or 2), -R b -S(O) t Ure a (wherein the formula t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2) can be substituted as needed, and each R b These are independently selected from directly bonded, linear, or branched alkylene, alkenylene, or alkynylene chains, and each R c These are linear or branched alkylene, alkenylene, or alkynylene chains.

[0054] The terms "as needed" or "as required" mean that the events or circumstances described thereafter may or may not occur, and that this description includes examples of when such events or circumstances occur and examples of when they do not. For example, "optionally substituted alkyl" means either "alkyl" or "substituted alkyl" as defined above. Furthermore, the optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted to a degree between fully substituted and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.).

[0055] The term “biomolecules” refers to biological components that may be involved in corona formation, including, but are not limited to, proteins, polypeptides, polysaccharides, sugars, lipids, lipoproteins, metabolites, oligonucleotides, metabolomes, or combinations thereof. A biomolecule corona of a distinct particle may contain several identical biomolecules, may contain distinct biomolecules with respect to other sensor elements, and / or the levels or amounts, types or arrangements of biomolecules bound to each sensor element may differ. In one embodiment, the biomolecules are selected from the group consisting of proteins, nucleic acids, lipids, and metabolomes.

[0056] It is understood that the ranges provided herein are concise for all values ​​within that range. For example, the range 1 to 50 is understood to include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as any number, combination of numbers, or subrange from the group consisting of all intervening decimal values ​​between the aforementioned integers, such as 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to subranges, "nested subranges" extending from any endpoint of the range are specifically intended. For example, nested subranges of the exemplary range 1-50 may include 1-10, 1-20, 1-30, and 1-40 in one direction, or 50-40, 50-30, 50-20, and 50-10 in the other direction.

[0057] The compounds and structures provided herein may be stereoisomers. In some cases, the compounds or structures of the disclosure may form stereoisomers. In some cases, the stereoisomers may be diastereomers (e.g., cis / trans isomers, E / Z isomers, conformational isomers, or rotational isomers). In some cases, the stereoisomers may be enantiomers (R,S enantiomers or + / - enantiomers). In some cases, the compounds or structures of the disclosure may be enanthopureous (e.g., 100% pure). In some cases, the compounds or structures may form a racemic mixture of enantiomers (e.g., 50% pure). In some cases, the compounds or structures of the Disclosure may be stabilized as stereoisomers, where the compounds or structures of the Disclosure constitute at least about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 98.5%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, about 99.9%, or more of a mixture of the compounds or structures and the corresponding stereoisomers. macromolecule structure

[0058] Macromolecular structures are provided herein, comprising a surface, anchoring sites coupled to the surface, and macromolecular chains. In some embodiments, the macromolecular structures provided herein include a surface and macromolecular chains. In some embodiments, the macromolecular structures provided herein include a surface. In some embodiments, the macromolecular structures provided herein include anchoring sites (e.g., coupled to the surface). In some embodiments, the macromolecular structures provided herein include macromolecular chains. In some embodiments, the first end of the macromolecular chain is covalently bonded to the anchoring site. In some embodiments, the second end of the macromolecular chain is not coupled to the surface. In some embodiments, the macromolecular chain comprises one or more (e.g., separate) repeating units derived from monomers.

[0059] In some embodiments, macromolecular structures are provided herein, comprising a surface, anchoring sites coupled to the surface, and macromolecular chains. In some embodiments, the macromolecular structure comprises a surface. In some embodiments, the macromolecular structure comprises anchoring sites (e.g., coupled to the surface). In some embodiments, the macromolecular structure comprises macromolecular chains. In some embodiments, the macromolecular chain comprises two or more distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain comprises at least two (e.g., at least three, at least four, at least five) distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain comprises up to ten (e.g., up to nine, up to eight, up to six, up to four, up to three) distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain comprises two distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain comprises three distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain comprises four distinct repeating units derived from different monomers. In some embodiments, the macromolecular chain contains five distinct repeating units derived from different monomers.

[0060] In some embodiments, macromolecular structures are provided herein, comprising a surface, anchoring sites coupled to the surface, and macromolecular chains. In some embodiments, the macromolecular structure comprises a surface. In some embodiments, the macromolecular structure comprises anchoring sites (e.g., coupled to the surface). In some embodiments, the macromolecular structure comprises macromolecular chains. In some embodiments, the macromolecular chain comprises repeating units derived from monomers. In some embodiments, the macromolecular chain is composed of a single monomer repeating unit.

[0061] In some applications, the tethering and repeating units used to functionalize a surface affect the physicochemical properties of the surface, such as size, surface charge, hydrophobicity, hydrophilicity, surface functionality, surface topography, surface curvature, porosity, shape, and any combination thereof. Changes in physicochemical properties can affect the binding properties of macromolecular structures to other compounds, such as biomolecules (e.g., proteins), leading to increased or decreased effectiveness in binding.

[0062] In some embodiments, the macromolecular structures provided herein include crosslinked polymers (e.g., crosslinked macromolecular chains). For example, the relative amount of crosslinked monomers to the total monomers in the polymer may be at least 0.1%, at least 0.5%, at least 1%, or at least 2% by weight or number. In some embodiments, the macromolecular structures provided herein include substantially uncrosslinked polymers (e.g., uncrosslinked macromolecular chains). For example, the relative amount of crosslinked monomers to the total monomers in the polymer may be less than 0.1%, less than 0.05%, less than 0.01%, or about 0% by weight or number. In some embodiments, the macromolecular structures provided herein include polymer brushes (e.g., PEG brushes). For example, a polymer brush may include side chains having at least 5, at least 10, at least 15, or at least 20 repeating units derived from one or more monomers.

[0063] In some embodiments, what is provided herein is a macromolecular structure comprising formula (A):ATC.

[0064] In some embodiments, A is a surface, for example, a surface provided elsewhere in this specification. In some embodiments, T is an anchoring site, for example, an anchoring site provided elsewhere in this specification. In some embodiments, C is a macromolecular chain, for example, a macromolecular chain provided elsewhere in this specification. In some embodiments, C comprises a plurality of repeating units derived from monomers. In some embodiments, the plurality of repeating units comprises a single monomer. In other embodiments, the plurality of repeating units comprises two or more different monomers. In some embodiments, the monomers have a controlled distribution across the macromolecular chain. In some embodiments, the monomers have a random distribution across the macromolecular chain.

[0065] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0066] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0067] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0068] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0069] In some embodiments, R 4 R is a C1-C6 alkyl group optionally substituted with hydrogen, sulfonate, carboxylate, C1-C4 alkylene, amine (e.g., quaternary ammonium cation), or halogen. In some embodiments, R 4 is hydrogen. In some embodiments, R 4 is absent. In some embodiments, R 4 is a sulfonate. In some embodiments, R 4 is an amine. In some embodiments, R 4 is a quaternary ammonium cation. In some embodiments, R 4 is a carboxylate. In some embodiments, R 4 These are C1-C4 alkylenes. In some embodiments, R 4 These are C1-C6 alkyl groups that are optionally substituted with halogens (e.g., haloalkyl groups).

[0070] In some embodiments, X is -C- or -N-. In some embodiments, X is -C-. In some embodiments, X is -N-.

[0071] In some embodiments, Y is -C- or -N-. In some embodiments, Y is -C-. In some embodiments, Y is -N-.

[0072] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0073] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0074] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0075] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0076] In some embodiments, R 9 is hydrogen or oxo. In some embodiments, R 9 is hydrogen. In some embodiments, R 9 It is oxo.

[0077] In some embodiments, X is -C- or -N-. In some embodiments, X is -C-. In some embodiments, X is -N-.

[0078] In some embodiments, Y is -C-, -N-, or -O-. In some embodiments, Y is -C-. In some embodiments, Y is -O-. In some embodiments, Y is -N-.

[0079] In some embodiments, [ka] This is a single bond or a double bond. In some embodiments, [ka] It is a single bond. In some embodiments, [ka] It is a double bond. In some embodiments, [ka] One of them is a single bond, [ka] One of them is a double bond. In some embodiments, both [ka] However, it is a single bond. In some embodiments, both [ka] However, it is a double bond.

[0080] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0081] In some embodiments, the repeating units are derived from acrylate monomers. In some embodiments, the repeating units are derived from methacrylate monomers.

[0082] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0083] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0084] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyl groups. In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with one or more methyl groups. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0085] In some embodiments, R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally further substituted (e.g., with two or more optionally further substituted condensed 6-membered rings); C1-C3 alkyls optionally substituted with benzyl, trimethoxysilane, or phosphorocoline; or C1-C4 alkylenes optionally substituted. In some embodiments, R 5 C1~C 12 It is an alkylamine.

[0086] In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is a C1-C6 alkyl group. In some embodiments, R 5 These are C1-C4 alkylenes. In some embodiments, R 5 These are C1-C8 alkyl groups, amines, azides, sulfonates, carbamates, asymmetric disulfides substituted with one or more hydroxyls, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl or oxo groups, or C1-C n1 It is ethylene glycol. In some embodiments, R 5 These are C1-C8 alkyl groups, amines, azides, carbamates, asymmetric disulfides substituted with one or more hydroxyls, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl or oxo groups, or C1-C n1 It is ethylene glycol. In some embodiments, R 5 is a C1-C8 alkylamine. In some embodiments, R 5 is a C1-C8 alkylamine substituted with an amine. In some embodiments, R 5 R is a C1-C8 alkylamine substituted with hydroxyl and amine. In some embodiments, 5 is a C1-C8 alkylamine substituted with a sulfonate. In some embodiments, R 5 is an aryl-substituted C1-C8 alkylamine. In some embodiments, R 5 is a C1-C8 alkoxy. In some embodiments, R 5 is a C1-C8 alkoxy substituted with one or more oxo or halogens. In some embodiments, R 5 is a C1-C8 alkoxy substituted with one or more oxos. In some embodiments, R 5 This is a C1-C8 alkoxy substituted with one or more halogens. In some embodiments, the alkylamine contains a quaternary ammonium cation.

[0087] In some embodiments, R 5 is one or more pyrene, two or more fused 5-6 member rings, optionally substituted with two or more fused 6-member rings (e.g., optionally substituted with two or more fused 6-member rings), optionally substituted with benzyl, trimethoxysilane, or optionally substituted with phosphorocoline, or optionally substituted with C1-C3 alkyl. In some embodiments, R 5 is a pyrene-substituted C1-C3 alkyl group. In some embodiments, R 5 is a C1-C3 alkyl group substituted with two or more 5-6 membered rings, which may be further substituted as needed, for example, two or more condensed 6-membered rings, which may be further substituted as needed. In some embodiments, R 5 is a C1-C3 alkyl group substituted with benzyl as needed. In some embodiments, R 5 is a C1-C3 alkyl substituted with trimethoxysilane. In some embodiments, R 5 These are C1-C3 alkyl groups substituted with phosphorocholine.

[0088] In some embodiments, R 5 is hydrogen, a C1-C6 alkyl, or pyrene, or a C1-C3 alkyl substituted with two or more fused 5-6 membered rings as needed. In some embodiments, R 5 The C1-C3 alkyl group is substituted with hydrogen, a C1-C6 alkyl group, or pyrene, or two or more substituted condensed 5-6 membered rings as needed, and the macromolecular chain contains two or more distinct repeating units.

[0089] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0090] In some embodiments, the repeating units are derived from acrylamide monomers.

[0091] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0092] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0093] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyl groups. In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with one or more methyl groups. In some embodiments, R 3 is 3,4-dimethyl-1H-pyrrole-2,5-dione. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0094] In some embodiments, R 6 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 6 is hydrogen. In some embodiments, R 6 These are C1-C6 alkyl groups.

[0095] In some embodiments, R 7C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 These are ethylene glycol, C1-C8 alkylamines further substituted with amines or sulfonates, C1-C8 alkoxys optionally substituted with one or more oxos or halogens, one or more pyrenes, two or more condensed 5-6 membered rings optionally substituted (e.g., two or more condensed 6-membered rings optionally substituted), optionally substituted benzyl, trimethoxysilane, or phosphorocoline-substituted -C1-C3 alkyls, or C1-C4 alkylenes.

[0096] In some embodiments, R 7 is hydrogen. In some embodiments, R 7 is a C1-C6 alkyl group. In some embodiments, R 7 These are C1-C4 alkylenes. In some embodiments, R 7 These are C1-C8 alkyl groups, amines, azides, sulfonates, carbamates, asymmetric disulfides substituted with one or more hydroxyls, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl or oxo groups, or C1-C n1 It is ethylene glycol. In some embodiments, R 7 These are C1-C8 alkyl groups, amines, azides, carbamates, asymmetric disulfides substituted with one or more hydroxyls, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl or oxo groups, or C1-C n1 It is ethylene glycol. In some embodiments, R 7 is a C1-C8 alkylamine. In some embodiments, R 7is a C1-C8 alkylamine substituted with an amine. In some embodiments, R 7 is a C1-C8 alkylamine substituted with a sulfonate. In some embodiments, R 7 is a C1-C8 alkoxy. In some embodiments, R 7 is a C1-C8 alkoxy substituted with one or more oxo or halogens. In some embodiments, R 7 is a C1-C8 alkoxy substituted with one or more oxos. In some embodiments, R 7 is a C1-C8 alkoxy substituted with one or more halogens. In some embodiments, R 7 These are C1-C6 alkyl groups that are optionally substituted with hydroxyl, substituted benzene, or hydrogen.

[0097] In some embodiments, R 7 is one or more pyrene, two or more fused 5-6 member rings, optionally substituted with two or more fused 6-member rings (e.g., optionally substituted with two or more fused 6-member rings), optionally substituted with benzyl, trimethoxysilane, or optionally substituted with phosphorocoline, or optionally substituted with C1-C3 alkyl. In some embodiments, R 7 is a pyrene-substituted C1-C3 alkyl group. In some embodiments, R 7 is a C1-C3 alkyl group substituted with two or more 5-6 membered rings, which may be further substituted as needed, for example, two or more condensed 6-membered rings, which may be further substituted as needed. In some embodiments, R 7 is a C1-C3 alkyl group substituted with benzyl as needed. In some embodiments, R 7 is a C1-C3 alkyl substituted with trimethoxysilane. In some embodiments, R 7 These are C1-C3 alkyl groups substituted with phosphorocholine.

[0098] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0099] In some embodiments, the repeating units derived from the monomer may be a diene, such as a cis-diene. In some embodiments, the diene may act as a crosslinking monomer.

[0100] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0101] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0102] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0103] In some embodiments, R 1’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1’ is hydrogen. In some embodiments, R 1’ These are C1-C6 alkyl groups.

[0104] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2’is hydrogen. In some embodiments, R 2’ These are C1-C6 alkyl groups.

[0105] In some embodiments, R 3’ R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3’ is hydrogen. In some embodiments, R 3’ is a C1-C6 alkyl group. In some embodiments, R 3’ It is methyl.

[0106] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0107] In some embodiments, the repeating units are derived from acrylonitrile monomers.

[0108] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0109] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0110] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0111] In some embodiments, R 1 is hydrogen, and R 2 is hydrogen, and R 3 It is hydrogen.

[0112] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0113] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0114] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0115] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0116] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0117] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0118] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0119] In some embodiments, R 6 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 6 is hydrogen. In some embodiments, R 6 is a C1-C6 alkyl group. In some embodiments, R 6 It is methyl.

[0120] In some embodiments, Q is -CH2- or ethylene glycol. In some embodiments, Q is -CH2-. In some embodiments, Q is ethylene glycol.

[0121] In some embodiments, m is 1 to 20. In some embodiments, m is 1 to 10. In some embodiments, m is 1 to 5. In some embodiments, m is 5 to 10. In some embodiments, m is 10 to 20. In some embodiments, m is 2. In some embodiments, m is 1. In some embodiments, m is 3, 4, 5, 6, 7, 8, 9, or 10.

[0122] In some embodiments, A is structure: [ka] This is a polymer side chain containing repeating units derived from monomers represented by [the symbol].

[0123] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0124] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0125] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0126] In some embodiments, R 1 is hydrogen, and R 2 is hydrogen, and R 3 It is hydrogen.

[0127] In some embodiments, R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1C1-C8 alkylamines optionally further substituted with ethylene glycol, amines, or sulfonates, C1-C8 alkoxys optionally substituted with one or more oxo or halogens, one or more pyrenes, optionally further substituted two or more condensed 5-6 membered rings, optionally substituted benzyl, trimethoxysilane, or phosphorocholine-substituted -C1-C3 alkyls, or C1-C4 alkylenes. In certain embodiments, R 5 is polyethylene glycol. In some embodiments, R 5 This is polyethylene glycol having a chain length of 9.

[0128] In some embodiments, R 1 is hydrogen, and R 2 is hydrogen, and R 3 Q is methyl, Q is -CH2-, and R 6 It is methyl, and R 5 It is polyethylene glycol.

[0129] In some embodiments, the macromolecular chains provided herein have the following structure: [ka] It contains repeating units derived from monomers represented by [the symbol].

[0130] In some embodiments, the repeating units are derived from dimethacrylate monomers. In some embodiments, the dimethacrylate monomers are crosslinked monomers.

[0131] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 is a C1-C6 alkyl group. In some embodiments, R 2 This is either hydrogen or a C1-C6 alkyl group.

[0132] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0133] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0134] In some embodiments, R 1’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1’ is hydrogen. In some embodiments, R 1’ These are C1-C6 alkyl groups.

[0135] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2’ is hydrogen. In some embodiments, R 2’ These are C1-C6 alkyl groups.

[0136] In some embodiments, R 3’ R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3’ is hydrogen. In some embodiments, R 3’ is a C1-C6 alkyl group. In some embodiments, R 3’ It is methyl.

[0137] In some embodiments, Z is -O- or -NH. In some embodiments, Z is -O-. In some embodiments, Z is -NH.

[0138] In some embodiments, R 8 is a C1-C6 alkyl, a divalent metal, or a symmetric or asymmetric disulfide. In some embodiments, R 8 is a C1-C6 alkyl group. In some embodiments, R 8 is a divalent metal. In some embodiments, R 8 is cadmium(II). In some embodiments, R 8 is a symmetric or asymmetric disulfide. In some embodiments, R 8 is a symmetric disulfide. In some embodiments, R 8 These are symmetric disulfides (e.g., CH2CH2S-SCH2CH2) or divalent metals.

[0139] In any of the macromolecular structures provided herein, n 1 n is an integer selected from 1 to 100. In some embodiments, n 1 n is an integer selected from 1 to 20. In some embodiments, n 1 n is an integer selected from 1 to 10. In some embodiments, n 1 n is an integer selected from 1 to 5. In some embodiments, n 1 n is an integer selected from 5 to 10. In some embodiments, n 1 n is an integer selected from 10 to 20. In some embodiments, n 1 is 9. In some embodiments, n 1 is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0140] In some embodiments, any of the macromolecular chains provided herein may be terminated with an end group. The end group may be a halogen, an epoxide, or an olefin (e.g., alkylene). In some embodiments, the end group is a halogen. In some embodiments, the end group is bromine. In some embodiments, the end group is iodine. In some embodiments, the end group is chlorine. In some embodiments, the end group is an epoxide. In some embodiments, the end group is an olefin.

[0141] In some embodiments, the macromolecular chains provided herein include repeating units derived from monomers represented by the structures in Table 1. In some embodiments, the macromolecular chains include two or more distinct repeating units derived from monomers represented by the structures in Table 1. [Table 1-1] [Table 1-2]

[0142] In some embodiments, the macromolecular chains provided herein include repeating units derived from monomers represented by the structures in Table 2. In some embodiments, the macromolecular chains include repeating units (e.g., one or more) derived from monomers represented by the structures in Table 2. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4]

[0143] In some embodiments, the repeating units provided herein are randomly distributed throughout the macromolecular chain. In some embodiments, the repeating units provided herein have a controlled distribution throughout the macromolecular chain. In some embodiments, the macromolecular chain is a homopolymer. In some embodiments, the macromolecular chain is a block copolymer. In some embodiments, the macromolecular chain is a random copolymer. Those skilled in the art, guided by the disclosure herein, will understand how to provide polymers having repeating units with a random or controlled distribution.

[0144] When multiple distinct repeating units are present in a macromolecular chain, these repeating units may be present in equal or different ratios. The ratio of distinct repeating units can be controlled according to methods known to those skilled in the art, which include the step of altering the stoichiometry of the added monomers.

[0145] In some embodiments, macromolecular structures are provided herein, comprising (I) a surface and (II) macromolecular chains coupled to the surface. In some embodiments, the macromolecular chains comprise repeating units of formula (I): [ka]

[0146] In some embodiments, R 1’’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1’’ is hydrogen. In some embodiments, R 1’’ is a C1-C6 alkyl group. In some embodiments, R 1’’ It is methyl.

[0147] In some embodiments, R 2’’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2’’ is a C1-C6 alkyl group. In some embodiments, R 2’’ It is methyl.

[0148] In some embodiments, R 3’’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 3’’ is hydrogen. In some embodiments, R 3’’ is a C1-C6 alkyl group. In some embodiments, R 3’’ It is methyl.

[0149] In some embodiments, R 1’’ , R 2’’ , and R 3’’These are C1-C6 alkyl groups (for example, methyl groups).

[0150] In some embodiments, n is an integer between 1 and 10,000. In some embodiments, n is an integer between 1 and 200. In some embodiments, n is an integer less than or equal to 25,000 (for example, less than or equal to 20,000, less than or equal to 15,000, less than or equal to 10,000, less than or equal to 5,000, less than or equal to 2,500, less than or equal to 1,000, less than or equal to 50, less than or equal to 100, less than or equal to 50). In some embodiments, n is an integer between 1 and 5,000. In some embodiments, n is an integer between 1 and 2,500. In some embodiments, n is an integer between 1 and 1,000. In some embodiments, n is an integer less than or equal to 200. In some embodiments, n is an integer between 1 and 100. In some embodiments, n is an integer between 1 and 50.

[0151] In some embodiments, A is a polymer side chain comprising one of the repeating units provided elsewhere in this specification. In some embodiments, A is poly(alkylene oxide) methacrylate or poly(alkylene oxide) acrylate. In some embodiments, A is poly(ethylene glycol) methacrylate or poly(ethylene glycol) acrylate. In some embodiments, A is poly(alkylene oxide) methacrylamide or poly(alkylene oxide) acrylamide. In some embodiments, A is poly(ethylene glycol) methacrylamide or poly(ethylene glycol) acrylamide.

[0152] In some embodiments, L is the linker portion. In some embodiments, the linker portion has the following structure: [ka] It is represented by [this].

[0153] In some embodiments, each Z is independently -O- or -N-. In some embodiments, Z is -O-. In some embodiments, Z is -N-.

[0154] In some embodiments, X' is a C1-C6 alkyl group. In some embodiments, X' is methyl. In some embodiments, X' is ethyl. In some embodiments, X' is propyl.

[0155] In some embodiments, the macromolecular structure further includes a crosslinking portion. In some embodiments, the crosslinking portion is [ka] Includes structures represented by

[0156] In some embodiments, the crosslinked portion is derived from a dimethacrylate monomer, for example, a dimethacrylate monomer described elsewhere in this specification. In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0157] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0158] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0159] In some embodiments, R 1’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1’is hydrogen. In some embodiments, R 1’ These are C1-C6 alkyl groups.

[0160] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2’ is hydrogen. In some embodiments, R 2’ These are C1-C6 alkyl groups.

[0161] In some embodiments, R 3’ R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3’ is hydrogen. In some embodiments, R 3’ is a C1-C6 alkyl group. In some embodiments, R 3’ It is methyl.

[0162] In some embodiments, Z is -O- or -NH. In some embodiments, Z is -O-. In some embodiments, Z is -NH.

[0163] In some embodiments, R 8 is a C1-C6 alkyl, a divalent metal, or a symmetric or asymmetric disulfide. In some embodiments, R 8 is a C1-C6 alkyl group. In some embodiments, R 8 is a divalent metal. In some embodiments, R 8 is cadmium(II). In some embodiments, R 8 is a symmetric or asymmetric disulfide. In some embodiments, R 8 It is a symmetric disulfide.

[0164] In some embodiments, the crosslinked portion is ethylene glycol dimethacrylate (EGDMA). In some embodiments, the crosslinked portion is ethylene glycol dimethylacrylamide. In some embodiments, the crosslinked portion is ethylene glycol diacrylate. In some embodiments, the crosslinked portion is ethylene glycol diacrylamide.

[0165] In some embodiments, the crosslinked portion is [ka] Includes structures represented by

[0166] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0167] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0168] In some embodiments, R 3 R is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0169] In some embodiments, R 4 The C1-C4 alkylene is used. In some embodiments, the crosslinked portion is divinylbenzene.

[0170] In some embodiments, the macromolecular structures provided herein include anchoring sites that couple the surface to the macromolecular chain. In some embodiments, the anchoring sites are C1-C6 alkyl, oxo, halo, or hydroxyl, as may be substituted as needed. 20 It is heteroalkyl.

[0171] In some embodiments, the mooring portion has the following structure: [ka] Includes.

[0172] In some embodiments, the mooring portion has the following structure: [ka] Includes.

[0173] In some embodiments, the mooring portion is one or more C1-C 20 C1-C as needed, substituted with heteroalkyl groups 12 It is an alkoxy, C1-C 12 Alkoxy and C1-C 20 Each heteroalkyl group is optionally substituted with one or more C1-C6 alkyl, oxo, halo, or hydroxyl groups. In some embodiments, the anchoring site is structured as follows: [ka] It is represented by [this].

[0174] In some embodiments, Y is C1~C 20 It is heteroalkyl. In some embodiments, Y is C1-C6 alkyl, oxo, halo, or hydroxyl as needed. 20 It is heteroalkyl.

[0175] In some embodiments, p is an integer from 1 to 12. In some embodiments, p is an integer from 1 to 6. In some embodiments, p is an integer from 1 to 3. In some embodiments, p is 3. In some embodiments, the mooring part is structured as follows: [ka] It is represented by [this].

[0176] In some embodiments, the mooring portion has the following structure: [ka] It is represented by [this].

[0177] In any of the macromolecular structures provided herein, R 5 or R 7 It may contain polyethylene glycol. In some embodiments, the polyethylene glycol may have a chain length of about 1 to about 50. In some embodiments, the polyethylene glycol may have a chain length of 100 or less. In some embodiments, the polyethylene glycol may have a chain length of at least 5. In some embodiments, the polyethylene glycol may have a chain length of about 5 to about 100, or about 5 to about 50. In some embodiments, the polyethylene glycol may have a chain length of about 9.

[0178] In some embodiments, the polyethylene glycol provided herein is oligoethylene glycol. In some embodiments, the polyethylene glycol is diethylene glycol. In some embodiments, the polyethylene glycol is triethylene glycol. In some embodiments, the polyethylene glycol is tetraethylene glycol.

[0179] In some embodiments, the macromolecular structures provided herein may have the structures shown in Table 3. [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4]

[0180] In some embodiments, in Table 3, "b" in any of the structures indicates a block copolymer structure. In some embodiments, the block copolymer structure depicted in Table 3 may be a random copolymer instead.

[0181] In any of the macromolecular structures provided herein, a macromolecular chain contains 1 to 1,000 repeating units. In some embodiments, a macromolecular chain contains at least 1, at least 10, at least 50, at least 100, at least 250, at least 500, at least 750, or at least 1,000 repeating units. In some embodiments, a macromolecular chain contains up to 2,500 repeating units. In some embodiments, a macromolecular chain contains up to 1,000 repeating units. In some embodiments, a macromolecular chain contains up to 750 repeating units. In some embodiments, a macromolecular chain contains up to 500 repeating units. In some embodiments, a macromolecular chain contains up to 250 repeating units. In some embodiments, a macromolecular chain contains up to 100 repeating units. In some embodiments, a macromolecular chain contains about 1 to about 100 repeating units. In some embodiments, a macromolecular chain contains about 1 to about 250 repeating units. In some embodiments, the macromolecular chain contains about 1 to about 500 repeating units. In some embodiments, the macromolecular chain contains about 1 to about 1,000 repeating units. In some embodiments, the macromolecular chain contains about 100 to about 1,000 repeating units. In some embodiments, the macromolecular chain contains about 1 to about 10 repeating units.

[0182] In any one of the macromolecular structures provided herein, the macromolecular chains contain molecular weights ranging from about 0.1 kDa to about 500 kDa. In some embodiments, the macromolecular chains contain molecular weights of at least 0.1 kDa, at least 1 kDa, at least 5 kDa, at least 10 kDa, at least 20 kDa, at least 25 kDa, at least 50 kDa, at least 100 kDa, at least 250 kDa, or at least 500 kDa. In some embodiments, the macromolecular chains contain molecular weights of 1000 kDa or less, 500 kDa or less, 750 kDa or less, 500 kDa or less, 250 kDa or less, 100 kDa or less, 75 kDa or less, 50 kDa or less, 40 kDa or less, 30 kDa or less, 25 kDa or less, 20 kDa or less, 15 kDa or less, or 10 kDa or less. In some embodiments, the macromolecular chains include molecular weights of approximately 0.1 to 500 kDa, 0.1 to 250 kDa, 0.1 to 100 kDa, 0.1 to 70 kDa, 0.5 to 10 kDa, 0.5 to 15 kDa, or 1 to 25 kDa. In some embodiments, the macromolecular chains include molecular weights of approximately 0.1 to 100 kDa. In some embodiments, the macromolecular chains include molecular weights of approximately 0.1 to 50 kDa.

[0183] In some embodiments, the macromolecular chain comprises a block copolymer. In some embodiments, the block copolymer comprises a first block derived from a first monomer and a second block derived from a second monomer, wherein the first block is adjacent to the anchoring site and the first monomer is more hydrophobic than the second monomer. In some embodiments, the block copolymer comprises a first block derived from a first monomer and a second block derived from a second monomer, wherein the first block is adjacent to the anchoring site and the first monomer is less hydrophobic than the second monomer. In some embodiments, the hydrophobicity of the first and second monomers can be determined by estimated partition coefficients using XLOGP3. In some embodiments, the absolute difference between the estimated partition coefficients of the first and second monomers is at least 0.3, at least 0.5, at least 0.8, at least 1, at least 1.5, or at least 2. In some embodiments, the absolute difference between the estimated partition coefficients of the first monomer and the second monomer is 3 or less, 2.5 or less, 2 or less, 1 or less, or 0.8 or less.

[0184] In some embodiments, the surface is a particle. In some embodiments, the particle is a nanoparticle or microparticle. In some embodiments, the particle is a nanoparticle. In some embodiments, the particle is a microparticle. In some examples, the particles provided herein have a diameter of at least 10 nm, at least 100 nm, at least 200 nm, at least 300 nm, at least 400 nm, at least 500 nm, at least 600 nm, at least 700 nm, at least 800 nm, or at least 900 nm. In some embodiments, the particles provided herein have a diameter of 5000 nm or less, 4000 nm or less, 3000 nm or less, 2000 nm or less, 1000 nm or less, 750 nm or less, or 500 nm or less. In some embodiments, the particles provided herein are 10nm-50nm, 50nm-100nm, 100nm-150nm, 150nm-200nm, 200nm-250nm, 250nm-300nm, 300nm-350nm, 350nm-400nm, 400nm-450nm, 450nm-500nm, 500nm-550nm, 550nm-600nm, 600nm-650nm, 650nm-700nm, 700nm-750nm, 750nm- The particles have diameters of 800 nm, 800 nm to 850 nm, 850 nm to 900 nm, 100 nm to 300 nm, 150 nm to 350 nm, 200 nm to 400 nm, 250 nm to 450 nm, 300 nm to 500 nm, 350 nm to 550 nm, 400 nm to 600 nm, 450 nm to 650 nm, 500 nm to 700 nm, 550 nm to 750 nm, 600 nm to 800 nm, 650 nm to 850 nm, 700 nm to 900 nm, or 10 nm to 900 nm. The particle size (e.g., diameter) can be measured by dynamic light scattering (DLS) as an indirect measure of size. DLS measurements can be "intensity-weighted" averages, meaning a size distribution where the average calculated therefrom can be weighted by the radius to the power of 6. This may be referred to herein as "z-average" or "intensity-average". Particle size can also be measured by electron microscopy (e.g., SEM, TEM).

[0185] In certain examples, the particles provided herein may have a diameter of about 100 nm to about 500 nm. In some embodiments, the particles have a diameter of about 100 nm to about 300 nm. In some embodiments, the particles have a diameter of about 100 nm to about 200 nm. In some embodiments, the particles have a diameter of about 150 nm to about 250 nm.

[0186] In addition, particles can have a uniform or heterogeneous size distribution. The polydispersity index (PDI), which can be measured by techniques such as dynamic light scattering, is a measure of the size distribution. A low PDI indicates a more uniform size distribution, while a higher PDI indicates a more heterogeneous size distribution. For example, the particles disclosed herein may have a PDI of less than 0.5, less than 0.4, less than 0.3, less than 0.2, less than 0.15, or less than 0.1. In certain embodiments, the particles disclosed herein have a PDI of less than 0.1. In some embodiments, the particles disclosed herein have a PDI greater than 0.5, greater than 1, or greater than 2.

[0187] The particles provided herein may have different surface charges within a range. The particles may be negatively charged, positively charged, or neutral. In some embodiments, the particles may have charges ranging from -150mV to -100mV, -100mV to -90mV, -90mV to -80mV, -80mV to -70mV, -70mV to -60mV, -60mV to -50mV, -50mV to -40mV, -40mV to -30mV, -30mV to -20mV, -20mV to -10mV, -10mV to 0mV, 0mV to 10mV, and 10mV. The particles have a surface charge of V~20mV, 20mV~30mV, 30mV~40mV, 40mV~50mV, 50mV~60mV, 60mV~70mV, 70mV~80mV, 80mV~90mV, 90mV~100mV, 100mV~110mV, 110mV~120mV, 120mV~130mV, 130mV~140mV, or 140mV~150mV. In some embodiments, the particles have a surface charge of about 0 to -100mV. In some embodiments, the particles have a surface charge of about 0 to 100mV. The charge can be determined in some embodiments by measuring the zeta potential at neutral pH using a suitable buffer solution.

[0188] Various particle morphologies are corresponding to the particle types of this disclosure. For example, the particles may be spherical, colloidal, quadrilateral, rod, wire, cone, pyramidal, or elliptical.

[0189] In some embodiments, the surface (e.g., particles) comprises any suitable material by those skilled in the art. In some embodiments, the particles are magnetic, e.g., any suitable magnetic material by those skilled in the art. In some embodiments, the particles comprises a metallic material. In some embodiments, the metallic material comprises any one or any combination thereof from gold, silver, copper, nickel, cobalt, palladium, platinum, iridium, osmium, rhodium, ruthenium, rhenium, vanadium, chromium, manganese, niobium, molybdenum, tungsten, tantalum, iron, and cadmium. In some embodiments, the particles comprises iron oxide. In some embodiments, the particles are superparamagnetic iron oxide particles. In some embodiments, the particles have a core-shell structure. In some embodiments, the particles have an iron oxide core. In some embodiments, the particles comprises a silica shell. In some embodiments, the particles comprise an iron oxide core with a silica shell. In some examples, the silica shell may be functionalized with anchoring sites or macromolecular chains provided elsewhere herein. In some embodiments, the particles comprises iron oxide crystals. In some embodiments, the particles comprise polystyrene. In some embodiments, the particles include iron oxide crystals embedded in a polystyrene core.

[0190] In some embodiments, the macromolecular structures provided herein include at least 5% w / w of repeating units provided herein. In some embodiments, the macromolecular structures include at least 10% w / w, at least 15% w / w, at least 20% w / w, at least 25% w / w, at least 30% w / w, at least 35% w / w, at least 40% w / w, at least 45% w / w, at least 50% w / w, at least 60% w / w, at least 75% w / w, at least 90% w / w, at least 95% w / w, at least 99% w / w, or about 100% w / w of repeating units provided herein. In some embodiments, the macromolecular structure includes repeating units provided herein in amounts of up to 95% w / w, up to 90% w / w, up to 85% w / w, up to 75% w / w, up to 70% w / w, up to 65% w / w, up to 60% w / w, up to 55% w / w, up to 50% w / w, up to 45% w / w, up to 40% w / w, up to 35% w / w, or up to 30% w / w. In some embodiments, the macromolecular structure includes repeating units provided herein in amounts of about 5% to about 95% w / w. In some embodiments, the macromolecular structure includes repeating units provided herein in amounts of about 5% to about 75% w / w. In some embodiments, the macromolecular structure includes repeating units provided herein in amounts of about 10% to about 50% w / w. In a particular embodiment, the macromolecular structure includes repeating units of at least 10% w / w. In certain embodiments, the macromolecular structure contains up to 50% w / w of repeating units. The weight percentage of repeating units in the macromolecular structure can be determined by thermogravimetric analysis (TGA).

[0191] In some embodiments, the surfaces provided herein include anchoring units (e.g., and macromolecular chains) at any suitable density by those skilled in the art. In some embodiments, the surfaces include at least 1 / 500 nm 2 It contains anchoring units (e.g., and macromolecular chains) at a density of . In some embodiments, the surface is at least 1 / 50 nm 2 It contains anchoring units (e.g., and macromolecular chains) at a density of . In some embodiments, the surface is at least 1 / 5 nm 2It contains anchoring units (e.g., and macromolecular chains) at a density of . In some embodiments, the surface is at least 1 / 1 nm 2 It contains anchoring units (e.g., and macromolecular chains) at a density of . In some embodiments, the surface is about 1 / 50 nm 2 ~about 1 / 5nm 2 It contains anchoring sites (e.g., and macromolecular chains) at a density of . Method of preparation

[0192] Methods for preparing any of the macromolecular structures provided herein are provided herein. In some embodiments, methods for preparing a macromolecular structure including a surface, anchoring sites, and the macromolecular structure itself are provided herein. Methods for preparing a macromolecular structure including a surface and a macromolecular chain of formula (I) are also provided herein.

[0193] In some embodiments, the methods provided herein include surface-initiated polymerization.

[0194] In some embodiments, the macromolecular structures provided herein further include end groups. In some embodiments, the end groups are halogens, epoxides, or alkylenes (e.g., olefins). In some embodiments, the end groups are halogens. In some embodiments, the end groups are bromine, chlorine, or iodine. In some embodiments, the end groups are bromine. In some embodiments, the end groups are involved in surface-initiated polymerization.

[0195] In some embodiments, methods for producing macromolecular structures, such as any macromolecular structures provided elsewhere in this specification, are provided herein. In some embodiments, the method includes the step of providing a surface. In some embodiments, the method further includes the step of coupling a polymer initiator to the surface to form an initiator surface. In some embodiments, the method further includes the step of contacting the initiator surface with a monomer, such as a monomer provided elsewhere in this specification, to form a macromolecular structure.

[0196] In some examples, exemplary synthesis schemes described by the methods provided herein are provided in Figure 1.

[0197] In some examples, the methods provided herein may also provide a block copolymer, for example, by contacting a second repeating unit with an initiator surface provided by a first repeating unit. An exemplary synthesis scheme illustrating this in detail is shown in Figure 7.

[0198] In some examples, the methods provided herein include the step of bringing an initiator surface into contact with one or more (different) monomers to form, for example, a heteropolymer. The monomers may consist of a controlled or random distribution. An exemplary synthesis scheme illustrating this in detail is shown in Figure 8.

[0199] In some embodiments, the method includes the step of providing a surface. The surface may include any surface (e.g., or particles) as described elsewhere in this specification. In some embodiments, the surface includes particles. In some embodiments, the particles are nanoparticles. In some embodiments, the particles are microparticles. In some embodiments, the surface includes silicon dioxide. In some embodiments, the surface is functionalized with an amine, for example, by functionalization with (3-aminopropyl)triethoxysilane (APTES). In some embodiments, the surface is functionalized with an epoxide using (3-glycidyloxypropyl)triethoxysilane, followed by a reaction with diaminohexane (Figure 6). Those skilled in the art will understand that surfaces can be functionalized using a variety of silane coupling agents and, as appropriate, further modified to achieve a variety of chain lengths and functionalizations. Non-exclusive examples of silane coupling agents include 3-aminopropyltriethoxysilane (APTES), 3-mercaptopropyltrimethoxysilane, 3-glycidoxypropyltrimethoxysilane (GPTMS), (3-triethoxysilylpropyl)diethylenetriamine (DETAS), N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, 3-isocyanatopropyltriethoxysilane, 3-chloropropyltrimethoxysilane, 3-bromopropyltrimethoxysilane, 3-iodopropyltrimethoxysilane, 3-[2-(2-aminoethylamino)ethylamino]propyl-dimethoxymethylsilane, 3-[2-(2-aminoethylamino)ethylaminopropyl]trimethoxysilane, propargyltriethoxysilane, 3-glycidyloxypropylheptamethyltrisiloxane, and 3-(2-(2-propynyloxy)ethoxy)propyltriethoxysilane.

[0200] In some embodiments, surface functionalization (e.g., silicon dioxide) is described in Example 1, where the silicon dioxide surface is functionalized with APTES via polymerization following, for example, amide coupling of a polymer initiator.

[0201] In some embodiments, the method further includes the step of coupling a polymer initiator to a surface to form an initiator surface. In some embodiments, the coupling step is completed using an organic solvent, for example, an organic solvent provided elsewhere herein. In some embodiments, the surface (e.g., particles) is in contact with or dispersed in the organic solvent before coupling. In some embodiments, the organic solvent includes dimethylformamide. In some embodiments, the organic solvent includes tetrahydrofuran. In some embodiments, the organic solvent includes N,N-dimethylacetamide.

[0202] In some embodiments, the coupling step further includes the addition of a base. In some embodiments, the base is a weak base. In some embodiments, the base is an amine. In some embodiments, the base is an alkylamine. In some embodiments, the base is a triethylamine.

[0203] In some embodiments, the coupling step is completed below room temperature. In some embodiments, the coupling step is completed at a temperature below 30°C. In some embodiments, the coupling step is completed at a temperature of 30°C or lower, 25°C or lower, 20°C or lower, 15°C or lower, 10°C or lower, 5°C or lower, or 0°C or lower. In some embodiments, the coupling step is completed above the freezing point of the solvent. In some embodiments, the coupling step is completed at a temperature of about 0°C to about 30°C. In some embodiments, the coupling step is completed at a temperature of about 0°C to about 15°C. In some embodiments, the coupling step includes a temperature of about -5°C to about 5°C. In some embodiments, the coupling step is completed at a temperature of about 0°C. In some embodiments, the coupling step is completed in an ice bath. In some examples, the reduced temperature is maintained during the addition of bases and polymer initiators.

[0204] In some embodiments, the polymer initiator is an oxo-substituted C1-C8 haloalkyl.

[0205] In some embodiments, the polymer initiator has the structure: [ka] It is represented by [this].

[0206] In some embodiments, X is a halogen. In some embodiments, X is bromine. In some embodiments, X is chlorine.

[0207] In some embodiments, R 10 is the initiator group. In some embodiments, the initiator group is a halogen. In some embodiments, the initiator group is bromine.

[0208] In some embodiments, the polymer initiator is 2-bromoisobutyryl bromide.

[0209] In some embodiments, the coupling step is performed for any preferred time by those skilled in the art, for example, to obtain a favorable yield of the product. In some embodiments, the coupling step is performed for at least 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, or 16 hours. In some embodiments, the coupling step is performed for a maximum of 36 hours, 24 hours, 20 hours, 18 hours, or 16 hours. In some embodiments, the coupling step is performed for about 0.5 hours to about 36 hours, or about 12 hours to about 20 hours. In some embodiments, the coupling step is performed for about 16 hours, for example, at 0°C.

[0210] In some embodiments, the coupling step is completed under inert conditions. In some embodiments, the coupling step is completed under N2 conditions.

[0211] In some embodiments, the coupling step further includes, for example, a washing step after the reaction. In some embodiments, the washing step includes washing with one or more organic or aqueous solvents. In some embodiments, the washing step includes washing separately with organic and aqueous solvents.

[0212] In some embodiments, non-limiting examples of organic solvents provided herein include ethanol, methanol, isopropanol, butanol, dimethyl sulfoxide, dimethylformamide, hexane, pentane, benzene, acetonitrile, acetone, carbon tetrachloride, chloroform, N,N-dimethylacetamide, cyclohexane, diethylene glycol, diethyl ether, ethyl acetate, and tetrahydrofuran. In some embodiments, the organic solvent is tetrahydrofuran. In some embodiments, the organic solvent is dimethylformamide. In some embodiments, the organic solvent is N,N-dimethylacetamide. In some embodiments, the organic solvent provided herein includes a combination of organic solvents. In some embodiments, the organic solvent provided herein includes a mixture of an organic solvent and water.

[0213] In some embodiments, an example of the coupling step is described in Example 2.

[0214] In some embodiments, the method includes the step of bringing the initiator surface into contact with a monomer to form a macromolecular structure. In some examples, the monomer is one of the monomers provided elsewhere in this specification.

[0215] In some embodiments, the contact step is completed under inert conditions. In some embodiments, the contact step is completed under N2 conditions.

[0216] In some embodiments, the method includes the step of dissolving the monomers separately in a solvent before adding them to the surface dispersion. In some embodiments, the solvent includes an organic solvent, such as dimethylformamide.

[0217] In some embodiments, the contact step includes sonication. In some embodiments, the solution is sonicated for at least 1 minute, at least 5 minutes, at least 10 minutes, or at least 15 minutes. In some embodiments, the solution is sonicated for 15 minutes.

[0218] In some embodiments, the contact step further includes the step of adding a reducing agent. In some embodiments, the reducing agent is L-ascorbic acid. In some embodiments, the reducing agent is added after the monomer has been added to the solution. In some embodiments, the reducing agent is added at a specified rate, for example, by a syringe pump. In some embodiments, the reducing agent is added in the range of about 0.05 mL / min. In some embodiments, the reducing agent is added at a rate of about 0.01 mL / min to about 0.5 mL / min.

[0219] In some embodiments, the contact step includes any preferred temperature by those skilled in the art. In some embodiments, the contact step includes a temperature of at least 25°C. In some embodiments, the contact step includes a temperature of at least 30°C, 40°C, 50°C, 60°C, or 70°C. In some embodiments, the contact step includes a temperature of the boiling point of the solvent or below the boiling point but above room temperature. In some embodiments, the contact step includes a temperature of about 25°C to about 75°C. In some embodiments, the contact step includes a temperature of about 35°C.

[0220] In some embodiments, the contact step is completed in an organic solvent, for example, an organic solvent described elsewhere herein. In some embodiments, the organic solvent is dimethylformamide (DMF), ethanol, methanol, i-propanol, dimethyl sulfoxide (DMSO), or a combination thereof or an aqueous mixture. In some embodiments, the contact step is completed in water. In some embodiments, the contact step is completed in dimethylformamide (DMF).

[0221] In some embodiments, methods for producing macromolecular structures are provided herein. In some embodiments, the method includes the step of providing a surface. In some embodiments, the method includes the step of coupling vinyl groups to the surface to form a vinyl-functionalized surface. In some embodiments, the method includes the step of contacting the vinyl-functionalized surface with a crosslinked monomer and a monomer selected from hydroxyalkyl methacrylate, aminoalkyl methacrylate, alkynyl methacrylate, glycidylalkyl methacrylate, hydroxyalkyl acrylate, aminoalkyl acrylate, alkynyl acrylate, or glycidylalkyl acrylate to form a crosslinked polymer coupled to the surface. In some embodiments, the method further includes the step of coupling a polymer initiator to the crosslinked polymer to form an initiator surface. In some embodiments, the method includes the step of contacting the initiator surface with a monomer, for example, a monomer provided elsewhere herein, to form a macromolecular structure.

[0222] In some examples, exemplary synthesis schemes described by the methods provided herein are provided in Figure 2. The vinyl-functionalized surface is subjected to polymerization in the presence of a diacrylamide crosslinking agent and a hydroxyalkyl methacrylate monomer. The polymer initiator is coupled to the hydroxyalkyl side chain of the crosslinked polymer. A second polymerization is carried out to incorporate an ethylene glycol methacrylate monomer.

[0223] In some embodiments, the method includes the step of providing a surface, for example, a surface provided elsewhere in this specification. In some embodiments, the surface is washed with a solvent, for example, an organic solvent, before the subsequent steps. In some embodiments, the surface contains silicon dioxide.

[0224] In some embodiments, the method includes the step of coupling vinyl groups to a surface to form a vinyl-functionalized surface. In some embodiments, the coupling step includes the step of dispersing the surface in a solvent. In some embodiments, the solvent is an organic solvent. In some embodiments, the solvent is dimethylformamide. In some embodiments, the dispersion is completed by sonication. In some embodiments, the vinyl group coupling step is completed under inert conditions. In some embodiments, the vinyl group coupling step is completed under N2. In some embodiments, the vinyl group coupling step is completed at a high temperature. In some embodiments, the vinyl group coupling step includes a temperature of at least 80°C. In some embodiments, the vinyl group coupling step includes a temperature of at least 90°C, 100°C, 110°C, or 120°C. In some embodiments, the vinyl group coupling step includes a step of heating to a maximum of 150°C, a maximum of 140°C, a maximum of 130°C, or a maximum of 120°C. In some embodiments, the vinyl group coupling step includes a step of heating to a temperature of about 120°C. In some embodiments, the coupling step further includes a washing step, for example, washing with an organic solvent (e.g., DMF).

[0225] In some embodiments, the method further includes the step of contacting a vinyl-functionalized surface with a crosslinked monomer and a monomer selected from hydroxyalkyl methacrylate, aminoalkyl methacrylate, alkynyl methacrylate, glycidylalkyl methacrylate, hydroxyalkyl acrylate, aminoalkyl acrylate, alkynyl acrylate, or glycidylalkyl acrylate to form a crosslinked polymer coupled to the surface. In some embodiments, the monomer is hydroxyalkyl methacrylate. In some embodiments, the monomer is aminoalkyl methacrylate. In some embodiments, the monomer is alkynyl methacrylate. In some embodiments, the monomer is glycidylalkyl methacrylate. In some embodiments, the monomer is hydroxyalkyl acrylate. In some embodiments, the monomer is aminoalkyl acrylate. In some embodiments, the monomer is alkynyl acrylate. In some embodiments, the monomer is glycidylalkyl acrylate. In some embodiments, the contacting step includes contacting steps described elsewhere in this specification. In some embodiments, the vinyl-functionalized surface includes vinyl acrylate.

[0226] In some embodiments, the crosslinked monomer is a diene. In some embodiments, the crosslinked monomer is ethylene glycol dimethacrylate (EGDMA). In some embodiments, the crosslinked monomer is divinylbenzene.

[0227] In some embodiments, the crosslinked monomer is [ka] Includes structures represented by

[0228] In some embodiments, R 1 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1 is hydrogen. In some embodiments, R 1 These are C1-C6 alkyl groups.

[0229] In some embodiments, R 2 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 These are C1-C6 alkyl groups.

[0230] In some embodiments, R 3 is hydrogen or a C1-C6 alkyl group. In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a C1-C6 alkyl group. In some embodiments, R 3 It is methyl.

[0231] In some embodiments, R 1’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 1’ is hydrogen. In some embodiments, R 1’ These are C1-C6 alkyl groups.

[0232] In some embodiments, R 2’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2’ is hydrogen. In some embodiments, R 2’ These are C1-C6 alkyl groups.

[0233] In some embodiments, R 3’ is hydrogen or a C1-C6 alkyl group. In some embodiments, R 3’ is hydrogen. In some embodiments, R 3’ is a C1-C6 alkyl group. In some embodiments, R 3’ It is methyl.

[0234] In some embodiments, the method further includes the step of coupling a polymer initiator to a crosslinked polymer to form an initiator surface. In some embodiments, the coupling step is described elsewhere in this specification. In some embodiments, the polymer initiator is a polymer initiator described elsewhere in this specification.

[0235] In some embodiments, the methods provided herein include polymerization. In some embodiments, the methods provided herein include surface-initiated polymerization. In some embodiments, the step of contacting the initiator surface includes polymerization. In some embodiments, the polymerization includes free radical polymerization. In other embodiments, the polymerization includes "living" / controlled free radical polymerization.

[0236] The methods provided herein may, in some embodiments, provide one of the macromolecular structures shown in Table 3. composition

[0237] In some embodiments, compositions comprising any one of the macromolecular structures provided herein are provided herein. In some embodiments, compositions comprising a macromolecular structure, e.g., a macromolecular structure provided elsewhere herein (e.g., including a surface, anchoring sites, and macromolecular chains), and a biomolecule are provided herein. In some embodiments, the biomolecule is adsorbed onto the macromolecular structure. In some embodiments, compositions comprising one or more macromolecular structures, e.g., a macromolecular structure provided elsewhere herein (e.g., including a surface, anchoring sites, and macromolecular chains), and a biomolecule adsorbed onto the macromolecular structure are provided herein.

[0238] In some embodiments, biomolecules adsorbed to a macromolecular structure form a biomolecular corona on the macromolecular structure.

[0239] In some embodiments, the compositions provided herein further comprise a biological sample in contact with a macromolecular structure. In some embodiments, the biological sample comprises a plurality of proteins. In some embodiments, the biological sample comprises plasma, serum, urine, cerebrospinal fluid, synovial fluid, tears, saliva, whole blood, milk, nipple aspirate, mammary duct lavage fluid, vaginal fluid, nasal fluid, ear fluid, gastric juice, pancreatic juice, trabecular meshwork, lung lavage fluid, sweat, gingival exudate, semen, prostatic fluid, sputum, fecal matter, bronchial lavage fluid, swab fluid, bronchial aspirate, fluid solid, fine needle aspiration sample, tissue homogenate, lymph fluid, cell culture sample, or any combination thereof. In some embodiments, the biological sample comprises plasma, serum, or blood. In some embodiments, the biological sample comprises blood. In some embodiments, the biological sample comprises plasma. In some embodiments, the biological sample comprises serum. In some embodiments, the biological sample is a biological fluid. In some embodiments, the biological sample is a cell-free sample.

[0240] In some embodiments, multiple biomolecules can be adsorbed onto the macromolecular structure provided herein. In some embodiments, multiple different biomolecules can be adsorbed onto the macromolecular structure provided herein. In some embodiments, at least 5, at least 10, at least 20, at least 40, at least 60, at least 80, at least 100, at least 200, at least 400, at least 600, at least 800, at least 1000, or at least 2000 (e.g., different) biomolecules are adsorbed onto the macromolecular structure provided herein. In some embodiments, up to 5000, up to 4000, up to 3000, up to 2000, up to 1000, up to 800, up to 600, up to 400, up to 200, up to 60, or up to 20 (e.g., different) biomolecules are adsorbed onto the macromolecular structure provided herein. In some embodiments, approximately 5 to approximately 5,000, approximately 10 to approximately 2,000, approximately 100 to approximately 2,000, or approximately 100 to approximately 1,000 (e.g., different) biomolecules are adsorbed onto the macromolecular structure provided herein. In some embodiments, at least 100 (e.g., different) biomolecules are adsorbed onto the macromolecular structure provided herein.

[0241] In some embodiments, the biomolecule is a protein, polypeptide, polysaccharide, sugar, lipid, lipoprotein, metabolite, oligonucleotide, or metabolome. In some embodiments, the biomolecule is a protein. In some embodiments, the biomolecule is a polypeptide. In some embodiments, the biomolecule is a polysaccharide. In some embodiments, the biomolecule is a sugar. In some embodiments, the biomolecule is a lipid. In some embodiments, the biomolecule is a lipoprotein. In some embodiments, the biomolecule is a metabolite. In some embodiments, the biomolecule is an oligonucleotide. In some embodiments, the biomolecule is a metabolome.

[0242] In some embodiments, compositions comprising macromolecular structures, for example, macromolecular structures provided herein (e.g., including surfaces, anchoring sites, and macromolecular chains), and proteins are provided herein. In some embodiments, compositions comprising one or more macromolecular structures, for example, macromolecular structures provided herein, and proteins are provided herein.

[0243] In some embodiments, multiple proteins can be adsorbed onto the macromolecular structure provided herein. In some embodiments, multiple different proteins can be adsorbed onto the macromolecular structure provided herein. In some embodiments, at least 5, at least 10, at least 20, at least 40, at least 60, at least 80, at least 100, at least 200, at least 400, at least 600, at least 800, at least 1000, or at least 2000 (e.g., different) proteins are adsorbed onto the macromolecular structure provided herein. In some embodiments, up to 5000, up to 4000, up to 3000, up to 2000, up to 1000, up to 800, up to 600, up to 400, up to 200, up to 100, or up to 20 (e.g., different) proteins are adsorbed onto the macromolecular structure provided herein. In some embodiments, approximately 5 to approximately 5,000, approximately 10 to approximately 2,000, approximately 100 to approximately 2,000, or approximately 100 to approximately 1,000 (e.g., different) proteins are adsorbed onto the macromolecular structure provided herein. In some embodiments, at least 100 (e.g., different) proteins are adsorbed onto the macromolecular structure provided herein. Methods for identifying proteins

[0244] Methods for identifying proteins in a sample having macromolecular structures (including, for example, surfaces, anchoring sites, and macromolecular chains) as provided elsewhere in this specification are provided herein. In some embodiments, the method includes the step of incubating one or more macromolecular structures with a biological sample containing biomolecules. In some embodiments, the step of incubating one or more macromolecular structures with a biological sample containing biomolecules results in the formation of a biomolecular corona. In some embodiments, the method includes the step of isolating at least a portion of the biomolecules in the biomolecular corona. In some embodiments, the method includes the step of assaying the biomolecular corona. In some embodiments, the biomolecules are biomolecules described elsewhere in this specification. In some embodiments, the biomolecules are proteins.

[0245] In some embodiments, the step of assaying the biomolecular coronavirus may be able to identify 1 to 50,000 protein groups or proteins. In some embodiments, 1 to 20,000 protein groups or proteins may be identified. In some embodiments, at least 100 protein groups may be identified. In some embodiments, at least 300 protein groups may be identified. In some embodiments, at least 500 protein groups may be identified. In some embodiments, at least 1,000 protein groups may be identified. In some embodiments, 1,000 to 10,000 protein groups or proteins may be identified. In some embodiments, 1,000 to 5,000 protein groups or proteins may be identified. In some embodiments, 1,800 to 5,000 protein groups or proteins may be identified. In some embodiments, 1,200 to 2,200 protein groups or proteins may be identified. In some embodiments, the protein groups or proteins may include peptide sequences having a minimum length of 2 amino acid residues. In some embodiments, the protein groups may include peptide sequences having a minimum length of 2 amino acid residues. In some embodiments, the protein group may include a peptide sequence having a minimum length of 5 amino acid residues. In some embodiments, the protein group may include a peptide sequence having a minimum length of 7 amino acid residues. In some embodiments, the protein group may include a peptide sequence having a minimum length of 8 amino acid residues. In some embodiments, the protein group may include a peptide sequence having a minimum length of 9 amino acid residues. In some embodiments, the protein group may include a peptide sequence having a minimum length of 10 amino acid residues. In some embodiments, the method may further include a step of lysing a protein of a separate biomolecule corona. In some embodiments, the method may further include a step of digesting a protein of a separate biomolecule corona. In some embodiments, the digested protein may be purified.

[0246] In some embodiments, the method further includes a step of repeating the method described herein, and if repeated, the incubation step, isolation step, and assay step result in a quantile normalization coefficient (QNCV) percentage of variation of 30% or less, determined by comparing peptide mass spectrometry characteristics from at least three complete assay repeats for each surface on one or more surfaces. In some embodiments, if repeated, the incubation step, isolation step, and assay step result in a quantile normalization coefficient (QNCV) percentage of variation of 25% or less, determined by comparing peptide mass spectrometry characteristics from at least three complete assay repeats for each surface on one or more surfaces. In some embodiments, if repeated, the incubation step, isolation step, and assay step result in a quantile normalization coefficient (QNCV) percentage of variation of 20% or less, determined by comparing peptide mass spectrometry characteristics from at least three complete assay repeats for each surface on one or more surfaces. In some embodiments, the assay step can identify proteins over a dynamic range of at least 6, at least 7, at least 8, at least 9, or at least 10. In some embodiments, the assay step can identify proteins over a dynamic range of 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, or 7 or less.

[0247] In some embodiments, the method may further include the step of washing one or more surfaces at least once after isolating them from unbound proteins. In some embodiments, the method may further include the step of washing one or more surfaces at least twice after isolating them from unbound proteins. In some embodiments, the method may further include the step of washing one or more surfaces at least three times after isolating them from unbound proteins. Isolation may be performed, for example, by magnetic isolation or centrifugation.

[0248] In some embodiments, the method may further include a step of desorbing proteins from the biomolecular coronavirus. In some embodiments, the method may further include a step of denaturing proteins from the biomolecular coronavirus.

[0249] In some embodiments, the methods of this specification further include a step of preparing an analyte (e.g., a protein) from a biomolecular corona for analysis. In some embodiments, the preparation of the analyte includes a step of digesting the biomolecular corona, a subset of biomolecules in the protein corona, or biomolecules desorbed from the biomolecular corona to form a digested sample. The step of preparing an analyte from a biomolecular corona for analysis may also include a step of chemically modifying the biomolecules derived from the biomolecular corona, for example, a step of methylating or reducing the biomolecules. In some embodiments, the step of preparing an analyte derived from a biomolecular corona for analysis may include a step of denaturing the analyte (e.g., a protein).

[0250] In some embodiments, the assay step includes identifying proteins in the sample using mass spectrometry. In some embodiments, the assay step includes using tandem mass spectrometry. In some embodiments, the assay step includes using liquid chromatography-tandem mass spectrometry. In some embodiments, the assay step may include ELISA, Edman degradation, immunoaffinity techniques, single-molecule protein sequencing, and the like.

[0251] In some embodiments, the assay step takes about 2 to 4 hours. In some embodiments, the method takes about 1 to 20 hours. In some embodiments, the method takes about 2 to 10 hours. In some embodiments, the method takes about 4 to 6 hours. In some embodiments, the isolation step takes about 30 minutes or less, about 15 minutes or less, about 10 minutes or less, about 5 minutes or less, or about 2 minutes or less.

[0252] In some embodiments, a plurality of spatially separated samples are processed according to the method. In some embodiments, the plurality of samples includes at least 10 spatially separated samples, at least 50 spatially separated samples, at least 100 spatially separated samples, at least 150 spatially separated samples, at least 200 spatially separated samples, at least 250 spatially separated samples, or at least 300 spatially separated samples. In further embodiments, the plurality of samples includes at least 96 samples.

[0253] In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure and a second distinct macromolecular structure, where the first distinct macromolecular structure and the second distinct macromolecular structure share at least one physicochemical property and differ by at least one physicochemical property, resulting in the first distinct macromolecular structure and the second distinct macromolecular structure being different. Both macromolecular structures may have polymeric properties, but different macromolecular structures can exhibit charge, for example, as measured by zeta potential analysis. In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure and a second distinct macromolecular structure, where the first distinct macromolecular structure and the second distinct macromolecular structure share at least two physicochemical properties and differ by at least two physicochemical properties, resulting in the first distinct macromolecular structure and the second distinct macromolecular structure being different. In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure share at least one physicochemical property and differ by at least two physicochemical properties, and as a result the first distinct macromolecular structure and the second distinct macromolecular structure are different.

[0254] In some embodiments, one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, wherein the first distinct macromolecular structure and the second distinct macromolecular structure share at least two physicochemical properties and differ by at least one physicochemical property, resulting in the first distinct macromolecular structure and the second distinct macromolecular structure being different. In further embodiments, the physicochemical properties include size, charge, core material, shell material, porosity, or macromolecular hydrophobicity. In further embodiments, the size is diameter or radius, measured by dynamic light scattering, SEM, TEM, or any combination thereof.

[0255] In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure having surface charges of 0 mV to -50 mV, and the first distinct macromolecular structure, the second distinct macromolecular structure, or both, having a diameter of less than 400 nm. In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure having diameters of 100 to 400 nm, the first distinct macromolecular structure having a positive surface charge, and the second distinct macromolecular structure having a negative surface charge.

[0256] In some embodiments, one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, where the first distinct macromolecular structure and the second distinct macromolecular structure are nanoparticles, the first distinct macromolecular structure having a surface charge of less than -20 mV, and the second distinct macromolecular structure having a surface charge of greater than 20 mV. In some embodiments, one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, where the first distinct macromolecular structure and the second distinct macromolecular structure are microparticles, the first distinct macromolecular structure having a negative surface charge, and the second distinct macromolecular structure having a positive surface charge. In some embodiments, one or more macromolecular structures comprise a subset of negatively charged nanoparticles, where each macromolecular structure in the subset differs by at least one surface chemical group. In some embodiments, one or more macromolecular structures include a first distinct macromolecular structure, a second distinct macromolecular structure, and a third distinct macromolecular structure, the first distinct macromolecular structure, the second distinct macromolecular structure, and the third distinct macromolecular structure each include an iron oxide core and have a diameter of less than approximately 500 nm, the first distinct macromolecular structure includes a negative charge of less than -40 mV, the second distinct macromolecular structure includes a positive charge of greater than 20 mV, and the third distinct macromolecular structure includes a negative charge of -20 mV to -40 mV.

[0257] In some embodiments, at least one of one or more distinct macromolecular structures comprises a carboxylated polymer, an amination polymer, a zwitterionic polymer, or any combination thereof.

[0258] In some embodiments, one or more macromolecular structures include at least two distinct macromolecular structures. In some embodiments, one or more macromolecular structures include at least three distinct macromolecular structures, at least four distinct macromolecular structures, at least five distinct macromolecular structures, at least six distinct macromolecular structures, at least seven distinct macromolecular structures, at least eight distinct macromolecular structures, at least nine distinct macromolecular structures, at least ten distinct macromolecular structures, at least eleven distinct macromolecular structures, at least twelve distinct macromolecular structures, at least thirteen distinct macromolecular structures, at least fourteen distinct macromolecular structures, at least fifteen distinct macromolecular structures, at least twenty distinct macromolecular structures, at least twenty-five distinct macromolecular structures, or at least thirty distinct macromolecular structures. In some embodiments, one or more macromolecular structures include up to fifty, up to 45, up to 40, up to 35, up to 30, up to 25, or up to 20 distinct macromolecular structures. In some embodiments, one or more macromolecular structures include about 2 to about 30 distinct macromolecular structures. In some embodiments, one or more macromolecular structures include at least 10 distinct macromolecular structures. Analysis and automated systems

[0259] In some embodiments, a system for identifying biomolecules in a biological sample is provided herein, which may include an automated system programmed to perform a series of steps, the system comprising (i) one or more macromolecular structures provided elsewhere herein; (ii) a biological sample containing biomolecules; and (iii) a network of units having distinct functions for isolating biomolecules adsorbed onto the macromolecular structures.

[0260] In some embodiments, a biological sample containing macromolecules immobilized on macromolecular structures provided elsewhere in this specification, suspensions, and proteins of a certain concentration may be incubated at a temperature of about 4 degrees Celsius (°C) to about 90 degrees Celsius. In some embodiments, one or more components of the composition may be incubated at a temperature of about 20 degrees Celsius to about 90 degrees Celsius. In some embodiments, one or more components of the composition may be incubated at a temperature of about 20 degrees Celsius to about 50 degrees Celsius. In some embodiments, one or more components of the composition may be incubated at a temperature of about 4 degrees Celsius to about 40 degrees Celsius. In some embodiments, one or more components of the composition may be incubated at a temperature of about 25 degrees Celsius to about 40 degrees Celsius.

[0261] In some embodiments, the suspension may contain Tris, EDTA, and CHAPS buffer. For example, the suspension may be Tris and EDTA in 150 mM KCl and 0.05% CHAPS buffer. In another example, the suspension may be 10 mM Tris HCl pH 7.4 and 1 mM EDTA.

[0262] In some embodiments, this disclosure provides an automated system including a network of units described in U.S. Patent No. 11,428,688, which is incorporated herein by reference in its entirety. In some embodiments, the network of units may include a distinguished function in identifying the state of a complex biological sample using multiple macromolecular structures having surfaces having different physicochemical properties, where a first unit includes a multichannel fluid transfer device for moving fluid between units in the system; a second unit includes a support for storing multiple biological samples; a third unit includes a support for a sensor array plate having compartments containing macromolecular structures for binding interactions with a population of analytes derived from the biological sample; a fourth unit includes a support for storing multiple reagents; a fifth unit includes a support for storing discarded reagents; a sixth unit includes a support for storing consumables used by the multichannel fluid transfer device; the system is programmed to perform a series of steps including: bringing a complex biological sample into contact with a specified compartment of the sensor array; incubating the complex biological sample with multiple macromolecular structures contained within the compartment of the sensor array plate; removing components from the compartment except for the multiple macromolecular structures and the population of analytes interacting with the macromolecular structures; and, if necessary, preparing a population of analytes for analysis, e.g., mass spectrometry.

[0263] In some embodiments, the first unit includes mobility that allows access to all other units in the system. In some embodiments, the first unit includes the ability to perform a pipetting function.

[0264] In some embodiments, the support of the second and / or third unit includes a support for a single plate, a 6-well plate, a 12-well plate, a 96-well plate, or a rack of microtubes. In some embodiments, the second and / or third unit includes a thermal unit capable of modulating the temperature of the support and the sample. In some embodiments, the second and / or third unit includes a rotating unit capable of physically stirring and / or mixing the sample.

[0265] In some embodiments, multiple macromolecular structures having surfaces with different physicochemical properties for binding to a population of analytes in a biological sample are immobilized on the macromolecular structures within a compartment of the sensor array. In some embodiments, multiple particles include multiple magnetic nanoparticles having different physicochemical properties for binding to a population of analytes in a complex biological sample. In some embodiments, the system includes the step of moving the sensor array plate to an additional seventh unit which includes a magnetized support and a thermal unit capable of modulating the temperature of the support and the sample, and incubating it for a further time.

[0266] In some embodiments, the fourth unit includes a set of reagents for generating a sensor array plate; washing unbound samples; and / or preparing samples for mass spectrometry. In some embodiments, the step of bringing a biological sample into contact with a specified section of the sensor array includes the step of pipetting a specified volume of the biological sample into a specific section of the sensor array.

[0267] In some embodiments, the step of bringing a biological sample into contact with a specified section of the sensor array includes the step of pipetting a volume of the biological sample of at least 10 microliters, at least 20 microliters, at least 50 microliters, at least 100 microliters, at least 250 microliters, at least 500 microliters, or at least 1000 microliters into a specific section of the sensor array. In some embodiments, the step of bringing a biological sample into contact with a specified section of the sensor array includes the step of pipetting a volume of 1000 microliters or less, 500 microliters or less, 250 microliters or less, 150 microliters or less, 100 microliters or less, 75 microliters or less, 50 microliters or less, or 30 microliters or less.

[0268] In some embodiments, the biological sample may be diluted with water or a buffer solution. In some embodiments, the biological sample may be diluted at least twice, at least three times, at least four times, or at least five times. In some embodiments, the biological sample may be diluted 20 times or less, 10 times or less, 8 times or less, or 5 times or less. In some embodiments, the biological sample is diluted about twice to about five times with water or a buffer solution.

[0269] In some embodiments, the step of incubating a biological sample with multiple macromolecular structures contained within a compartment of a sensor array plate is performed for at least about 10 seconds, at least about 15 seconds, at least about 20 seconds, at least about 25 seconds, at least about 30 seconds, at least about 40 seconds, at least about 50 seconds, at least about 60 seconds, at least about 90 seconds, at least about 2 minutes, at least about 3 minutes, at least about 4 minutes, at least about 5 minutes, at least about 6 minutes, at least about 7 minutes, at least about 8 minutes, at least about 9 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 minutes, at least about The incubation time includes 25 minutes, at least about 30 minutes, at least about 45 minutes, at least about 50 minutes, at least about 60 minutes, at least about 90 minutes, at least about 2 hours, at least about 3 hours, at least about 4 hours, at least about 5 hours, at least about 6 hours, at least about 7 hours, at least about 8 hours, at least about 9 hours, at least about 10 hours, at least about 12 hours, at least about 14 hours, at least about 15 hours, at least about 16 hours, at least about 17 hours, at least about 18 hours, at least about 19 hours, at least about 20 hours, or at least about 24 hours. In some embodiments, the step of incubating a biological sample with multiple macromolecular structures contained within a compartment of a sensor array plate includes an incubation time of 24 hours or less, 12 hours or less, 6 hours or less, 3 hours or less, 2 hours or less, 90 minutes or less, 75 minutes or less, 60 minutes or less, 45 minutes or less, or 30 minutes or less. In some embodiments, the step of incubating a biological sample with multiple macromolecular structures contained within a compartment of a sensor array plate includes incubation times of 30 minutes and 3 hours.

[0270] In some embodiments, the step of incubating a biological sample with multiple macromolecular structures contained within a compartment of the substrate includes an incubation temperature of approximately 4°C to approximately 40°C. The step of incubating a biological sample with multiple macromolecular structures contained within a compartment of the substrate may include an incubation temperature of approximately 4°C to approximately 37°C. The step of incubating a biological sample with multiple macromolecular structures contained within a compartment of the substrate may include an incubation temperature of approximately 20°C to approximately 50°C. The step of incubating a biological sample with multiple macromolecular structures contained within a compartment of the substrate may include an incubation temperature of approximately 4°C to approximately 100°C.

[0271] In some embodiments, the second unit may facilitate the transfer of the sample to the mass spectrometry unit for mass spectrometry.

[0272] In some embodiments, the Disclosure provides an automated apparatus for identifying proteins in a biological sample, comprising a sample preparation unit; a substrate containing multiple channels; multiple pipettes; multiple solutions; and multiple macromolecular structures as described herein. In some embodiments, the automated apparatus is configured to form a protein corona and digest the protein corona.

[0273] In some embodiments, the automated apparatus further includes a magnetic source. In some embodiments, the automated apparatus is configured for BCA, gel, or trypsin digestion of protein corona.

[0274] In some embodiments, the automated device is sealed. In some embodiments, the automated device is sterilized before use. In some embodiments, the automated device is configured for mass spectrometry. In some embodiments, the automated device is temperature-controlled.

[0275] Proteomics data of a sample can be identified, measured, and quantified using several different analytical techniques. For example, proteomics data can be analyzed using SDS-PAGE or any gel-based separation technique. Peptides and proteins can also be identified, measured, and quantified using immunoassays, such as ELISA. Alternatively, proteomics data can be identified, measured, and quantified using mass spectrometry, high-performance liquid chromatography, LC-MS / MS, Edman degradation, immunoaffinity techniques, and the methods disclosed in EP3548652, WO2019083856, WO2019133892, each of which is incorporated herein by reference in whole, as well as other protein separation techniques.

[0276] In some embodiments, the Disclosure provides an automated apparatus for generating a subset of biomolecules from a biological sample, comprising a substrate having multiple compartments, a first unit containing the biological sample, and a loading unit that is movable across the substrate and capable of moving volumes (e.g., volumes of buffer) between different units of the apparatus. In some cases, the substrate is a multiwell plate.

[0277] Multiple compartments may include multiple sensor elements. Multiple sensor elements may include surfaces. Multiple sensor elements may be macromolecular structures (e.g., particles) as disclosed herein. For example, a sensor element may include a first distinct nanoparticle and a second distinct nanoparticle.

[0278] A compartment within a group of compartments may contain 1 to 100 types of sensor elements (e.g., separate macromolecular structures). A compartment within a group of compartments may contain 2 to 50 types of sensor elements. A compartment within a group of compartments may contain 2 to 20 types of sensor elements. A compartment within a group of compartments may contain 2 to 5 types of sensor elements. A compartment within a group of compartments may contain 3 to 8 types of sensor elements. A compartment within a group of compartments may contain 4 to 10 types of sensor elements. A compartment within a group of compartments may contain 5 to 12 types of sensor elements. A compartment within a group of compartments may contain 6 to 15 types of sensor elements. A compartment within a group of compartments may contain 8 to 20 types of sensor elements. A compartment within a group of compartments may contain 2 types of sensor elements. A compartment within a group of compartments may contain 3 types of sensor elements. A compartment within a group of compartments may contain 4 types of sensor elements. A compartment within a group of compartments may contain 1 type of sensor element.

[0279] Two or more sections from among multiple sections may contain different quantities of sensor elements. Two or more sections from among multiple sections may contain different types of sensor elements. Sections within multiple sections may contain different combinations of sensor element types and / or quantities than other sections within the multiple. Subsets of sections within multiple sections may each contain distinct combinations of sensor elements that are separate from other sections within the multiple.

[0280] The sensor elements may be stored in a dry form inside or within the compartment. The dry sensor elements may be reconstituted or rehydrated before use. The sensor elements may also be stored in a solution. For example, the substrate compartment may contain a solution containing a high concentration of macromolecular structures.

[0281] The compartments within the multiple compartments may contain sensor elements of different concentrations or amounts (e.g., by mass / moles per unit volume of the sample). The compartments within the multiple compartments may contain sensor elements of 1 pM to 100 nM. The compartments within the multiple compartments may contain sensor elements of 1 pM to 500 pM. The compartments within the multiple compartments may contain sensor elements of 10 pM to 1 nM. The compartments within the multiple compartments may contain sensor elements of 100 pM to 10 nM. The compartments within the multiple compartments may contain sensor elements of 500 pM to 100 nM. The compartments within the multiple compartments may contain sensor elements of 50 μg / ml to 300 μg / ml. The compartments within the multiple compartments may contain sensor elements of 100 μg / ml to 500 μg / ml. The compartments within the multiple compartments may contain sensor elements of 250 μg / ml to 750 μg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration of 400 μg / ml to 1 mg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration of 600 μg / ml to 1.5 mg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration of 800 μg / ml to 2 mg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration of 1 mg / ml to 3 mg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration of 2 mg / ml to 5 mg / ml. A compartment selected from multiple compartments may contain a sensor element with a concentration exceeding 5 mg / ml.

[0282] A loading unit may be configured to move a volume (e.g., a volume of solution or powder) between any unit, compartment, or section within the apparatus. A loading unit may be configured to move a precise volume (e.g., within 0.1%, 0.01%, or 0.001% of a specified volume). A loading unit may be configured to collect a volume from a substrate or a compartment or section within a substrate and dispense the volume back into the substrate or a compartment or section within a substrate, or to dispense a volume or a portion of a volume into a different unit, compartment, or section. A loading unit may be configured to move multiple volumes simultaneously, for example, 2 to 400 separate volumes. A loading unit may include multiple pipette tips.

[0283] The loading unit may be configured to move the volume of liquid. The volume may be approximately 0.1 μl, 0.2 μl, 0.3 μl, 0.4 μl, 0.5 μl, 0.6 μl, 0.7 μl, 0.8 μl, 0.9 μl, 1 μl, 2 μl, 3 μl, 4 μl, 5 μl, 6 μl, 7 μl, 8 μl, 9 μl, 10 μl, 12 μl, 15 μl, 20 μl, 25 μl, 30 μl, 40 μl, 50 μl, 60 μl, 70 μl, 80 μl, 90 μl, 100 μl, 120 μl, 150 μl, 180 μl, 200 μl, 250 μl, 300 μl, 400 μl, 500 μl, 600 μl, 800 μl, 1 ml, or more than 1 ml. The liquid may be a biological sample or a solution.

[0284] In some cases, the solution includes washing solutions, resuspension solutions, denaturation solutions, buffers, reagents (e.g., reducing reagents), or any combination thereof. In some cases, the solution includes biological samples.

[0285] In some cases, these features may enable the loading unit to compartmentalize the sample. In some embodiments, this involves dividing the sample into several compartments. The sample can be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180, 200, 250, 300, 350, 400, 500, or more compartments. The sample can be divided into 96, 192, or 384 compartments. The automated device may include multiple substrates containing compartments. The automated device may include 1, 2, 3, 4, 5, or more substrates containing compartments. In some cases, the loading unit loads different volumes of a biological sample into different compartments. In some cases, the loading unit loads the same volume into two or more compartments. The volume of the biological sample loaded into the compartment may be approximately 0.1 μl, 0.2 μl, 0.3 μl, 0.4 μl, 0.5 μl, 0.6 μl, 0.7 μl, 0.8 μl, 0.9 μl, 1 μl, 2 μl, 3 μl, 4 μl, 5 μl, 6 μl, 7 μl, 8 μl, 9 μl, 10 μl, 12 μl, 15 μl, 20 μl, 25 μl, 30 μl, 40 μl, 50 μl, 60 μl, 70 μl, 80 μl, 90 μl, 100 μl, 120 μl, 150 μl, 180 μl, 200 μl, 250 μl, 300 μl, 400 μl, 500 μl, 600 μl, 800 μl, 1 ml, or more than 1 ml. The volume of the biological sample loaded into the compartment may be approximately 10 μl to 400 μl. The volume of the biological sample loaded into the compartment may be approximately 5 μl to 150 μl. The volume of the biological sample loaded into the compartment may be approximately 35 μl to 80 μl. In some cases, the loading unit may compartmentalize two or more biological samples. For example, a sample storage unit may contain two biological samples that the system compartmentalizes into one well plate. In some embodiments, the loading unit can facilitate the transfer of the sample to the mass spectrometry unit for mass spectrometry.

[0286] The system may be configured to perform dilution in the sample or sample compartment. The sample or sample compartment may be diluted with buffer, water (e.g., purified water), a non-aqueous solvent, or any combination thereof. The dilutions may be stored in the automated device before dispensing into the substrate compartment. The automated device may store multiple dilutions with different pH, salinity, osmotic pressure, viscosity, dielectric constant, or any combination thereof. The dilutions may be used to adjust the chemical properties of the sample or sample compartment. The automated device may dilute the sample or sample compartment by 2, 3, 4, 5, 6, 8, 10, 15, 20, 30, 40, 50, 75, 100, 150, 200, 300, 400, 500 times, or more. In some embodiments, the automated device may dilute the sample or sample compartment by about 2 to about 5 times. The automated device may perform different dilutions for two samples or sample compartments. The system may perform different dilutions on each of the 96 sample compartments within a multi-compartment system. For example, the system may perform different dilutions on each of the 96 sample compartments in a 96-well plate. In some cases, the different dilutions include dilutions of different degrees (e.g., 2x versus 4x). In some cases, the different dilutions include dilutions with different solutions (e.g., different buffers). In some cases, two sample compartments may be prepared to differ in one or more chemical properties, such as pH, salinity, or viscosity.

[0287] In some cases, the system may modify the chemical composition of the sample or sample compartment. The system may modify or adjust the pH, salinity, osmotic pressure, dielectric constant, viscosity, type of buffer, type of salt, type of sugar, type of detergent, or any combination thereof for the sample or sample compartment. Such modifications or adjustments may include mixing reagents from the fourth unit with the sample or sample compartment. The system may modify the chemical composition of two samples or sample compartments differently.

[0288] The systems or automated apparatus of this disclosure may also include incubation elements. An incubation element may contact, support, or hold another component of the automated apparatus (e.g., a substrate or unit). An incubation unit may contact, support, or hold multiple components of the automated apparatus. An incubation element may be in contact with a substrate to facilitate heat transfer between the incubation element and the substrate. An incubation unit may be configured to control the temperature of one or more components of the automated apparatus, for example, by heating or cooling. An incubation element may be capable of cooling a component of the apparatus from 20°C to 1°C. An incubation element may be capable of heating a component of the apparatus from 25°C to 100°C. An incubation element may be capable of setting the temperature of a component of the apparatus between 4°C and 37°C. An incubation element may be configured to heat or cool different parts of a component of the automated apparatus to different temperatures. For example, an incubation element may maintain a first compartment in the substrate at 30°C and a second compartment in the substrate at 35°C. The incubation element may control the temperature of the sample or compartment. The incubation element may include a temperature sensor (e.g., a thermocouple) for detecting the temperature inside the compartment or container. The incubation element may adjust its heating or cooling in response to readings from the temperature sensor.

[0289] The incubation element may be configured to physically agitate the components of the automated device. The agitation may take the form of shaking or rotation, vibration, shaking, ultrasonic treatment, or any combination thereof. The incubation element may be capable of providing multiple agitation intensities and / or frequencies. For example, the incubation element may include multiple settings for shaking at different frequencies and amplitudes. The incubation element may also be capable of agitating and / or mixing a volume (e.g., a portion of a biological sample).

[0290] The automated apparatus may include a unit containing a resuspension solution. The loading unit may be capable of moving a volume of resuspension solution from one of several compartments of the substrate into a compartment. In some cases, this may result in dilution of the sample present in the compartment and further desorption of multiple biomolecules from the biomolecular corona placed on the sensor element within the compartment. The amount of biomolecules desorbed from the biomolecular corona may depend on the volume of resuspension solution added to the compartment, the temperature of the compartment, the composition of the resuspension solution (e.g., salinity, osmotic pressure, viscosity, dielectric constant, or pH), the volume of the biological sample in the compartment, the type of sensor element, and the composition of biomolecules in the biomolecular corona. The movement of a volume of resuspension solution into a compartment may result in the desorption of less than 5% of biomolecules from the biomolecular corona. The movement of a volume of resuspension solution into a compartment may result in the desorption of 10% to 20% of biomolecules from the biomolecular corona. The movement of a volume of resuspension solution into a compartment may result in the desorption of 20% to 30% of biomolecules from the biomolecular corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 30% to 40% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 40% to 50% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 50% to 60% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 60% to 70% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 70% to 80% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of 80% to 90% of biomolecules from the biomolecule corona. The transfer of volume of resuspended solution into the compartment may result in the desorption of more than 90% of biomolecules from the biomolecule corona.

[0291] In some cases, multiple desorption rounds are performed. In each round, the supernatant containing the desorbed biomolecules may be collected, analyzed, or discarded. The types and amounts of biomolecules in the supernatant may differ between desorption rounds. The automated system may perform one or more desorption and discard cycles (i.e., washing), followed by one or more desorption cycles including sample collection and / or analysis.

[0292] The resuspension solution may be adapted to optimize the enrichment of a specific biomarker. The resuspension solution may contain a buffer, e.g., Tris-EDTA(TE), CHAPS, PBS, citrate, HEPES, MES, CHES, or another biobuffer. The resuspension solution may contain Tris EDTA(TE), 150 mM KCl, and 0.05% CHAPS buffer. The resuspension solution may contain 10 mM TrisHCl, pH 7.4, and 1 mM EDTA. The resuspension solution may also contain, or may not contain, highly purified water (e.g., distilled or deionized water). Desorption of biomolecules may be amplified by heating or stirring with an incubation element. The supernatant may be transferred to a new compartment after desorption. The resuspension solution may be used to dilute the sample.

[0293] The automated apparatus may include a unit containing a denaturation solution. The denaturation solution may contain a protease. The denaturation solution may contain a chemical capable of peptide cleavage (e.g., cyanogen bromide, formic acid, or hydroxylamine, 2-nitro-5-thiocyanatobenzoic acid). The denaturation solution may contain a chemical denaturant, such as guanidine, urea, sodium deoxycholate, acetonitrile, trichloroacetic acid, acetic acid, sulfosalicylic acid, sodium bicarbonate, ethanol, perchlorate, dodecyl sulfate, or any combination thereof. The denaturation solution may contain a reducing agent, such as 2-mercaptoethanol, dithiothreitol, or tris(2-carboxyethyl)phosphine. The protease may be trypsin. The denaturation solution may be added to the compartment after desorption. The denaturation solution may be added to the compartment containing the biomolecule corona.

[0294] The automated device may include a magnet or an array of magnets. The automated device may be capable of moving the substrate on and from the magnet or array of magnets. The array of magnets may be structured such that multiple magnets from the array of magnets can be positioned directly below multiple compartments on the substrate. The magnet may be capable of immobilizing magnetic sensor elements (e.g., magnetic particles, e.g., coated or uncoated superparamagnetic iron oxide nanoparticles) within compartments on the substrate. For example, the magnet may prevent magnetic nanoparticles from being removed from the compartments during the washing step. The magnet may also produce pellets from the magnetic particle collection. The magnet may produce particle pellets in less than 10 minutes. The magnet may produce particle pellets in less than 5 minutes. The particle pellets may contain particles having a biomolecular corona.

[0295] The automated apparatus may include a purification unit. The purification unit may include a plurality of compartments containing an adsorbent or resin. The purification unit may include a solid-phase extraction array or plate. The solid-phase extraction array or plate may contain a polar stationary phase material. The solid-phase extraction array or plate may contain a non-polar stationary phase material. The solid-phase extraction array or plate may contain a C18 stationary phase material (e.g., octadecyl silica gel). The automated apparatus may include a unit having a conditioning solution for the purification unit (e.g., a conditioning solution for the solid-phase extraction material). The automated apparatus may include a unit having an elution solution for removing biomolecules from the purification unit.

[0296] In some embodiments, the supernatant is removed from the sensor array plate. In some examples, an automated system may perform a series of washing steps. The washing steps may remove biomolecules not bound to the sensor elements in the compartment. The washing steps may desorb a subset of biomolecules bound to the sensor elements in the compartment. For example, the washing steps may result in the desorption and removal of a subset of soft corona analytes while leaving most of the hard corona analytes bound to the sensor elements intact.

[0297] In some embodiments, the Disclosure provides an automated apparatus for identifying proteins in a biological sample, wherein the automated apparatus comprises a sample preparation unit; a substrate containing multiple channels; multiple pipettes; multiple solutions; multiple macromolecular structures, e.g., macromolecular structures provided elsewhere herein, and is configured to form and digest protein coronas.

[0298] In some embodiments, the automated apparatus further includes a magnetic source. In some embodiments, the automated apparatus is configured for BCA, gel, or trypsin digestion of protein corona.

[0299] In some embodiments, the automated device is sealed. In some embodiments, the automated device is sterilized before use. In some embodiments, the automated device is configured for mass spectrometry. In some embodiments, the automated device is temperature-controlled. kit

[0300] In one embodiment, a kit for identifying biomolecules in a biological sample is described herein, the kit may include one or more macromolecular structures as described elsewhere herein. In some embodiments, the kit may be used to perform a method for identifying proteins in a sample provided herein. In some embodiments, the kit may be configured to perform the method using an automated apparatus provided herein.

[0301] The kits of this disclosure may include one or more macromolecular structures (e.g., particles) for examining a sample. The kits may be pre-packaged in individual aliquots. In another example, the kit may include one or more different macromolecular structures (e.g., particles having different surface chemistry) that can be used to examine a sample. Multiple different macromolecular structures may be pre-packaged, where each of the multiple macromolecular structures is packaged separately. Alternatively, multiple macromolecular structures may be packaged together so as to contain a combination of macromolecular structures in a single package. In some embodiments, the kit includes two or more packages containing different macromolecular structures (e.g., particles), and at least one of the packages contains two or more different macromolecular structures (e.g., particles). In some embodiments, the macromolecular structures (e.g., particles) may be lyophilized and stored in a sealed container.

[0302] In some embodiments, the kit further comprises a denaturing agent. In some embodiments, the denaturing agent comprises at least one of the following: sodium dodecyl sulfate, acetic acid, trichloroacetic acid, sulfosalicylic acid, sodium bicarbonate, ethanol, formaldehyde, glutaraldehyde, urea, guanidinium chloride, lithium perchlorate, 2-mercaptoethanol, dithiothreitol, tris(2-carboxyethyl)phosphine (TCEP), or any combination thereof.

[0303] In some embodiments, the kit further comprises a reducing agent. In some embodiments, the reducing agent comprises TCEP, dithiothreitol, beta-mercaptoethanol, glutathione, cysteine, or any combination thereof.

[0304] In some embodiments, the kit further comprises an alkylating agent. In some embodiments, the alkylating agent includes iodoacetamide, iodoacetic acid, acrylamide, chloroacetamide, or any combination thereof.

[0305] In some embodiments, the kit further comprises a digestive agent. In some embodiments, the digestive agent comprises trypsin, lysine, serine protease, or any combination thereof.

[0306] In some embodiments, the kit further comprises an elution buffer. In some embodiments, the elution buffer comprises triethylammonium bicarbonate, tris(hydroxymethyl)aminomethane, citrate, Tris, phosphate, ethylenediaminetetraacetic acid, or any combination thereof.

[0307] In some embodiments, the kit further includes a cleaning agent. In some embodiments, the cleaning agent is water or a buffer solution.

[0308] In some embodiments, the kit further includes a solid support for solid-phase extraction. In some embodiments, the kit includes a polar stationary phase material. In some embodiments, the kit includes a non-polar stationary phase material. In some embodiments, the kit includes a C18 stationary phase material (e.g., octadecyl silica gel). In some embodiments, the kit includes a conditioning solution for the solid-phase extraction material.

[0309] In some embodiments, the kit further includes a multiwell plate. In some embodiments, the multiwell plate is a 4-well plate. In some embodiments, the multiwell plate is a 12-well plate. In some embodiments, the multiwell plate is a 24-well plate. In some embodiments, the multiwell plate is a 48-well plate. In some embodiments, the multiwell plate is a 96-well plate. In some embodiments, the multiwell plate is a 384-well plate. In some embodiments, the multiwell plate is a 1536-well plate.

[0310] In some embodiments, the kit further includes a diluent. In some embodiments, the diluent is an organic solvent. In some embodiments, the diluent is water. In some embodiments, the diluent is a buffer solution. In some embodiments, the diluent is an organic solvent, water, a buffer solution, or any combination thereof.

[0311] In some embodiments, the kit further comprises an organic solvent. In some embodiments, the kit further comprises a cysteine ​​blocking reagent. In some embodiments, the cysteine ​​blocking reagent comprises methylmethanethiosulfonate, iodoacetamide, N-ethylmaleimide, methylsulfonylbenzothiazole, or any combination thereof. Numbered Embodiments

[0312] Numbered embodiments 1 to 271 are provided herein. Embodiment 1. A macromolecular structure, (I) surface; (II) Mooring portions coupled to the surface; and (III) Macromolecule chain It contains, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain, [ka] [ka] [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH; Q is -CH2- or ethylene glycol; A is structure: [ka] A polymer side chain containing repeating units derived from a monomer represented by; m is an integer selected from 1 to 20; [ka] It is either a single bond or a double bond; R 1 , R 2 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups; R 4 These are C1-C6 alkyl groups that are absent, hydrogen, sulfonates, carboxylates, C1-C4 alkylenes, amines, quaternary ammonium cations, or C1-C6 alkyl groups substituted as needed with halogens; R 5C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines optionally further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally further substituted with two or more condensed 5-6 membered rings; optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; C1-C3 alkyls optionally substituted with phosphorocholine. 12 Alkylamines, or C1-C4 alkylenes; R 6 is hydrogen or a C1-C6 alkyl group. R 7 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines optionally further substituted with ethylene glycol, amines, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes; two or more condensed 5-6 membered rings optionally further substituted; -C1-C3 alkyls optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; or C1-C4 alkylenes. R 8 These are C1-C6 alkyl groups, divalent metals, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1[This is an integer selected from 1 to 100.] A macromolecular structure comprising two or more distinct repeating units derived from monomers represented by a structure selected from the group consisting of the following. Embodiment 2. Macromolecular chain, structure: [ka] A macromolecular structure according to Embodiment 1, comprising repeating units derived from monomers represented by Embodiment 3. R 1 However, the macromolecular structure is hydrogen, as described in Embodiment 1 or 2. Embodiment 4. R 2 However, the macromolecular structure is hydrogen, as described in any one of Embodiments 1 to 3. Embodiment 5. R 3 However, the macromolecular structure is hydrogen, as described in any one of Embodiments 1 to 4. Embodiment 6. R 5 The macromolecular structure according to any one of Embodiments 1 to 5, wherein the C1-C3 alkyl group is substituted with hydrogen, a C1-C6 alkyl group, or pyrene, or two or more substituted condensed 5-6 membered rings as needed. Embodiment 7. R 3 However, the macromolecular structure is methyl, as described in any one of Embodiments 1 to 4. Embodiment 8. R 5 However, C1~C n1 The macromolecular structure described in Embodiment 7 is ethylene glycol. Embodiment 9. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of Embodiments 1 to 8, comprising repeating units derived from monomers represented by Embodiment 10. R 1 However, the macromolecular structure described in Embodiment 9 is hydrogen. Embodiment 11. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 9 or 10. Embodiment 12. R 3 However, the macromolecular structure is H as described in any one of embodiments 9 to 11. Embodiment 13. R 3 However, the macromolecular structure according to any one of embodiments 9 to 11 is a 3, 5, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyl groups. Embodiment 14. R 6 However, the macromolecular structure is H as described in any one of embodiments 9 to 13. Embodiment 15. R 7 The macromolecular structure according to any one of Embodiments 9 to 14, wherein the macromolecular structure is a hydroxyl, substituted benzene, or C1-C6 alkyl group optionally substituted with hydrogen. Embodiment 16. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 15, comprising repeating units derived from monomers represented by . Embodiment 17. R 1 However, the macromolecular structure described in Embodiment 16 is hydrogen. Embodiment 18. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 16 or 17. Embodiment 19. R 1’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 16 to 18. Embodiment 20. R 2’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 16 to 19. Embodiment 21. R 3 However, the macromolecular structure is methyl, as described in any one of embodiments 16 to 20. Embodiment 22. R 3’ However, the macromolecular structure is methyl, as described in any one of embodiments 16 to 21. Embodiment 23. A macromolecular structure according to any one of Embodiments 16 to 22, wherein each Z is O. Embodiment 24. R8 However, the macromolecular structure is C1-C6 alkyl, as described in any one of embodiments 16-23. Embodiment 25. R 8 The macromolecular structure according to any one of embodiments 16 to 23, wherein the molecule is a symmetric disulfide (e.g., CH2CH2S-SCH2CH2) or a divalent metal. Embodiment 26. R 3 However, the macromolecular structure is hydrogen, as described in any one of embodiments 16 to 20. Embodiment 27. R 3’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 16 to 20. Embodiment 28. A macromolecular structure according to either Embodiment 26 or 27, wherein each Z is -N-. Embodiment 29. R 8 However, the macromolecular structure is C1-C6 alkyl, as described in any one of embodiments 26-28. Embodiment 30. A macromolecular structure, (I) surface; (II) Mooring portions coupled to the surface; and (III) Macromolecule chain It contains, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain, [ka] [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH; Q is -CH2- or ethylene glycol; A is structure: [ka] A polymer side chain containing repeating units derived from a monomer represented by; m is between 1 and 6; R 1 , R 2 , R 1’ , R2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups; R 4 These are C1-C6 alkyl, C1-C4 alkylene, C1-C6 alkyl, sulfonate, amine, quaternary ammonium cation, or carboxylate, which are absent, substituted as needed with hydrogen, or halogens; R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally substituted (e.g., two or more fused 6-membered rings optionally substituted); two or more fused 5-6 membered rings optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; C1-C3 alkyls optionally substituted with phosphorocholine. 12 Alkylamines, or C1-C4 alkylenes; R 6 These are hydrogen or linear C1-C6 alkyl groups. R 7 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1C1-C8 alkylamines further substituted with ethylene glycol, amines or sulfonates, C1-C8 alkoxys optionally substituted with one or more oxo or halogens, one or more pyrenes, two or more condensed 5- or 6-membered rings optionally further substituted (e.g., two or more condensed 6-membered rings optionally further substituted), optionally substituted benzyl, trimethoxysilane, or phosphorocholine-substituted -C1-C3 alkyls, or C1-C4 alkylenes; R 8 These are C1-C6 alkyl groups, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1 is an integer selected from 1 to 100; However, R 3 If it is CH3, then R 4 is CH3, or R 5 If C1-C8 alkyl is substituted with hydroxyl, then C1-C8 is further substituted. A macromolecular structure containing repeating units derived from monomers, represented by a structure selected from the group consisting of the following. Embodiment 31. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 30, comprising repeating units derived from monomers represented by . Embodiment 32. The macromolecular structure according to Embodiment 31, wherein Q is -CH2-. Embodiment 33. R 1 However, the macromolecular structure is hydrogen, as described in Embodiment 31 or 32. Embodiment 34. R 2 However, the macromolecular structure is hydrogen, as described in any one of embodiments 31 to 33. Embodiment 35. R 3 However, the macromolecular structure is methyl, as described in any one of embodiments 31 to 34. Embodiment 36. A macromolecular structure according to any one of Embodiments 31 to 35, wherein m is 2. Embodiment 37. R 6 However, the macromolecular structure is a C1-C6 alkyl group, as described in any one of embodiments 31-36. Embodiment 38. The macromolecular structure according to Embodiment 31, wherein Q is ethylene glycol. Embodiment 39. R 1 However, the macromolecular structure described in Embodiment 38 is hydrogen. Embodiment 40. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 38 or 39. Embodiment 41. R 6 However, the macromolecular structure is C1-C6 alkyl, as described in any one of embodiments 38-40. Embodiment 42. R 5 However, C1~C n1 A macromolecular structure according to any one of embodiments 38 to 41, wherein the macromolecular structure is ethylene glycol. Embodiment 43. A macromolecular structure, (I) A macromolecular structure comprising a surface and (II) macromolecular chains coupled to the surface, wherein the macromolecular chains contain repeating units of formula (I): [ka] [In the formula, R 1’’ , R 2’’ , and R 3’’ Each of them is independently either hydrogen or a C1-C6 alkyl group; L is the linker part; A is [ka] A polymer side chain containing repeating units derived from monomers represented by a structure selected from the group consisting of the following: Each of X and Y is independently -C-, -O-, or -N-; Z is -O- or -NH; R 1, R 2 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; R 3 is a 3, 5, or 6-membered heterocycle optionally substituted with hydrogen, a C1-C6 alkyl group, or one or more C1-C6 alkyl groups; R 4 These are C1-C6 alkyl groups that are absent, hydrogen, sulfonates, carboxylates, C1-C4 alkylenes, amines, quaternary ammonium cations, or C1-C6 alkyl groups substituted as needed with halogens; R 5 C1-C6 alkyl groups, C1-C8 alkyl groups substituted with one or more hydroxyls, amines, azides, sulfonates, carbamate esters, asymmetric disulfides, 3, 5, or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl groups or oxos, or C1-C n1 C1-C8 alkylamines further substituted with ethylene glycol, amines, hydroxyl, aryl, or sulfonates; C1-C8 alkoxys optionally substituted with one or more oxo or halogens; one or more pyrenes optionally substituted (e.g., two or more fused 6-membered rings optionally substituted); two or more fused 5-6 membered rings optionally substituted with benzyl, trimethoxysilane, or phosphorocholine; C1-C3 alkyls optionally substituted with phosphorocholine. 12 Alkylamines, or C1-C4 alkylenes; R 6 These are hydrogen or linear C1-C6 alkyl groups. R 7 These are hydrogen, C1-C6 alkyl, a 3, 5, or 6-membered heterocycle optionally substituted with one or more C1-C6 alkyl or oxo, a substituted benzene, a hydroxyl-substituted C1-C6 alkyl, or an optionally substituted C1-C8 alkyl sulfonate; R 8These are C1-C6 alkyl groups, divalent metals, or symmetric or asymmetric disulfides; R 9 is hydrogen or oxo; n 1 is an integer selected from 1 to 100; n is an integer selected from 1 to 10,000. Embodiment 44. The linker portion has the following structure: [ka] [In the formula, Each Z is independently either O or N; X' is a C1-C6 alkyl group. The macromolecular structure described in Embodiment 43, represented by [the specified symbol]. Embodiment 45. The macromolecule structure according to Embodiment 43 or 44, wherein the macromolecule further includes anchoring sites. Embodiment 46. A macromolecular structure according to any one of Embodiments 43 to 45, wherein the macromolecular structure further comprises a crosslinking portion. Embodiment 47. The crosslinked portion is [ka] [In the formula, R 1 , R 2 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; Z is -O- or -NH; R 8 [These are C1-C6 alkyl, divalent metal, symmetric or asymmetric disulfide compounds.] A macromolecular structure according to Embodiment 46, including a structure represented by [the given symbol]. Embodiment 48. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of Embodiments 1 to 47, comprising repeating units derived from monomers represented by . Embodiment 49. R 1 However, the macromolecular structure described in Embodiment 48 is H. Embodiment 50. R 2 However, the macromolecular structure is H as described in Embodiment 48 or 49. Embodiment 51. R 3 However, the macromolecular structure is H as described in any one of embodiments 48 to 50. Embodiment 52. R 4 The macromolecular structure according to any one of embodiments 48 to 51, wherein the C1-C6 alkyl group is optionally substituted with a halogen, absence, hydrogen, carboxylate, or sulfonate. Embodiment 53. R 4 However, the macromolecular structure is a C1-C4 alkylene as described in any one of embodiments 48-51. Embodiment 54. A macromolecular structure according to any one of Embodiments 48 to 53, wherein X is -C- or -N-. Embodiment 55. A macromolecular structure according to any one of Embodiments 48 to 54, wherein Y is -C- or -N-. Embodiment 56. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of Embodiments 1 to 55, comprising repeating units derived from monomers represented by . Embodiment 57. R 1 However, the macromolecular structure described in Embodiment 56 is H. Embodiment 58. R 2 However, the macromolecular structure is H as described in embodiment 56 or 57. Embodiment 59. R 3 However, the macromolecular structure is H as described in any one of embodiments 56 to 58. Embodiment 60. R 5The macromolecular structure according to any one of embodiments 56 to 59, wherein the C1 alkyl, pyrene-substituted C1-C3 alkyl, optionally further substituted C1-C3 alkyl containing two or more condensed 5-6 membered rings, or H. Embodiment 61. R 3 However, the macromolecular structure is methyl, as described in any one of embodiments 56 to 58. Embodiment 62. R 5 However, H, C2-C6 alkyl, C1-C6 alkyl substituted with one or more hydroxyls, amine, azide, asymmetric disulfide, 3, 5 or 6-membered heterocycles optionally substituted with one or more C1-C6 alkyl or oxo, or C1-C n1 The macromolecular structure according to Embodiment 61, which is an ethylene glycol, a C1-C8 alkylamine further substituted with an amine or sulfonate, a C1-C8 alkoxy optionally substituted with one or more oxo or halogens, one or more pyrenes, two or more condensed 5-6 membered rings optionally substituted with trimethoxysilanes, or a -C1-C3 alkyl or C1-C4 alkylene optionally substituted with phosphorocholine. Embodiment 63. R 5 However, C1~C n1 The macromolecular structure described in Embodiment 61 is ethylene glycol. Embodiment 64. R 5 However, in the case of a hydroxyl-substituted C1-C6 alkyl group, the macromolecular structure according to Embodiment 61 is characterized in that the C1-C6 alkyl group is substituted with at least one further hydroxyl or azide group. Embodiment 65. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 64, comprising repeating units derived from monomers represented by . Embodiment 66. R 1 However, the macromolecular structure described in Embodiment 65 is H. Embodiment 67. R 2 However, the macromolecular structure is H as described in embodiment 65 or 66. Embodiment 68. R 3 The macromolecular structure according to any one of embodiments 65 to 67, wherein the macromolecular structure is a 3, 5, or 6-membered heterocycle optionally substituted with H or one or more C1-C6 alkyl groups. Embodiment 69. R 6 The macromolecular structure according to any one of embodiments 65 to 68, wherein the macromolecular structure is a 3, 5, or 6-membered heterocycle optionally substituted with H or one or more C1-C6 alkyl groups. Embodiment 70. R 7 The macromolecular structure according to any one of embodiments 65 to 69, wherein the macromolecular structure is a C1-C2 alkyl, hydroxyl, substituted benzene, or hydrogen-substituted -C1-C6 alkyl. Embodiment 71. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 70, comprising repeating units derived from monomers represented by Embodiment 72. R 1 However, the macromolecular structure described in Embodiment 71 is hydrogen. Embodiment 73. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 71 or 72. Embodiment 74. R 3 However, the macromolecular structure is hydrogen, as described in any one of embodiments 71 to 73. Embodiment 75. [ka] However, the macromolecular structure is a double bond, as described in any one of embodiments 71 to 74. Embodiment 76. A macromolecular structure according to any one of Embodiments 71 to 75, wherein X is -N-. Embodiment 77. A macromolecular structure according to any one of Embodiments 71 to 76, wherein Y is -N-. Embodiment 78. R 9 However, the macromolecular structure is hydrogen, as described in any one of embodiments 71 to 77. Embodiment 79. [ka] However, the macromolecular structure is a single bond as described in any one of embodiments 71 to 74. Embodiment 80. The macromolecular structure according to Embodiment 79, wherein X is -N-. Embodiment 81. The macromolecular structure according to Embodiment 79 or 80, wherein Y is -C-. Embodiment 82. R 9 However, the macromolecular structure described in any one of embodiments 79 to 81 is an oxo. Embodiment 83. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of Embodiments 1 to 82, comprising repeating units derived from monomers represented by Embodiment 84. The macromolecular structure according to Embodiment 83, wherein X is -O-. Embodiment 85. R 1 However, the macromolecular structure is hydrogen, as described in Embodiment 83 or 84. Embodiment 86. R 2 However, the macromolecular structure is hydrogen, as described in any one of embodiments 83 to 85. Embodiment 87. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 86, comprising repeating units derived from monomers represented by Embodiment 88. R 1 However, the macromolecular structure described in Embodiment 87 is hydrogen. Embodiment 89. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 87 or 88. Embodiment 90. R 3However, the macromolecular structure is hydrogen, as described in any one of embodiments 87 to 89. Embodiment 91. R 3’ However, the macromolecular structure is methyl, as described in any one of embodiments 87 to 90. Embodiment 92. R 1’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 87 to 91. Embodiment 93. R 2’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 87 to 92. Embodiment 94. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 93, comprising repeating units derived from monomers represented by . Embodiment 95. R 1 However, the macromolecular structure described in Embodiment 94 is hydrogen. Embodiment 96. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 94 or 95. Embodiment 97. R 3 However, the macromolecular structure is hydrogen, as described in any one of embodiments 94 to 96. Embodiment 98. Macromolecular chain, structure: [ka] A macromolecular structure according to any one of embodiments 1 to 97, comprising repeating units derived from monomers represented by . Embodiment 99. R 1 However, the macromolecular structure described in Embodiment 98 is hydrogen. Embodiment 100. R 2 However, the macromolecular structure is hydrogen, as described in Embodiment 98 or 99. Embodiment 101. R 1’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 98 to 100. Embodiment 102. R 2’However, the macromolecular structure is hydrogen, as described in any one of embodiments 98 to 101. Embodiment 103. R 3 However, the macromolecular structure is methyl, as described in any one of embodiments 98 to 102. Embodiment 104. R 3’ However, the macromolecular structure is methyl, as described in any one of embodiments 98 to 103. Embodiment 105. A macromolecular structure according to any one of Embodiments 98 to 104, wherein Z is O. Embodiment 106. R 8 However, the macromolecular structure is C1-C6 alkyl, as described in any one of embodiments 98-105. Embodiment 107. R 8 However, the macromolecular structure is a symmetric disulfide (e.g., CH2CH2S-SCH2CH2) as described in any one of embodiments 98 to 105. Embodiment 108. R 3 However, the macromolecular structure is hydrogen, as described in any one of embodiments 98 to 102. Embodiment 109. R 3’ However, the macromolecular structure is hydrogen, as described in any one of embodiments 98 to 102. Embodiment 110. A macromolecular structure according to either Embodiment 108 or 109, wherein Z is -N-. Embodiment 111. R 8 However, the macromolecular structure is a C1-C6 alkyl group, as described in any one of embodiments 108-110. Embodiment 112. A macromolecular structure according to any one of Embodiments 1 to 111, wherein the macromolecular chain comprises repeating units derived from monomers represented by the structures in Table 1. Embodiment 113. A macromolecular structure according to any one of Embodiments 1 to 112, wherein the macromolecular chain comprises repeating units derived from monomers represented by the structures in Table 2. Embodiment 114. A macromolecular structure, [ka] [ka] A macromolecular structure according to any one of embodiments 1 to 113, having the structure represented by [the given formula]. Embodiment 115. A macromolecular structure according to any one of Embodiments 1 to 114, wherein the surface contains particles. Embodiment 116. The macromolecular structure according to Embodiment 115, wherein the particles are nanoparticles. Embodiment 117. The macromolecular structure according to Embodiment 115, wherein the particles are microparticles. Embodiment 118. A macromolecular structure according to any one of Embodiments 115 to 117, wherein the particles have a diameter of approximately 100 nm to approximately 500 nm. Embodiment 119. A macromolecular structure according to any one of Embodiments 115 to 118, wherein the particles have a diameter of approximately 100 nm to approximately 300 nm. Embodiment 120. A macromolecular structure according to any one of Embodiments 115 to 119, wherein the particles have a polydispersity index (PDI) of about 0.01 to about 1. Embodiment 121. A macromolecular structure according to any one of Embodiments 115 to 120, wherein the particles contain a PDI of less than about 0.1. Embodiment 122. A macromolecular structure according to any one of Embodiments 115 to 121, wherein the particles contain iron oxide. Embodiment 123. A macromolecular structure according to any one of Embodiments 115 to 122, wherein the particles have an iron oxide core. Embodiment 124. A macromolecule according to any one of Embodiments 115 to 123, wherein the particles are magnetic. Embodiment 125. A macromolecular structure according to any one of Embodiments 115 to 124, wherein the particles are superparamagnetic iron oxide particles. Embodiment 126. A macromolecular structure according to any one of Embodiments 115 to 125, wherein the particles have a core-shell structure. Embodiment 127. A macromolecular structure according to any one of Embodiments 115 to 126, wherein the particles comprise an iron oxide core having a silica shell. Embodiment 128. A macromolecular structure according to any one of Embodiments 115 to 126, wherein the particles include iron oxide crystals embedded in a polystyrene core. Embodiment 129. A macromolecular structure according to any one of Embodiments 1 to 128, comprising at least 10% w / w repeating units. Embodiment 130. A macromolecular structure according to any one of Embodiments 1 to 129, comprising up to 50% w / w repeating units. Embodiment 131. A macromolecular structure according to any one of Embodiments 1 to 130, wherein the anchoring portion is covalently coupled to the surface. Embodiment 132. A macromolecular structure according to any one of Embodiments 1 to 131, wherein the anchoring site is coupled to the surface by a non-covalent bond. Embodiment 133. The anchoring site is a C1-C6 alkyl, oxo, halo, or hydroxyl atom, which may be substituted as needed. 20 A macromolecular structure according to any one of embodiments 1 to 132, which is a heteroalkyl group. Embodiment 134. The mooring section has the following structure: [ka] The macromolecular structure described in Embodiment 133, represented by [the specified symbol]. Embodiment 135. The mooring section has the following structure: [ka] A macromolecular structure as described in any one of embodiments 1 to 132, represented by [the specified symbol]. Embodiment 136. The mooring area is one or more C1-C 20 C1-C as needed, substituted with heteroalkyl groups 12 It is an alkoxy, C1-C 12 Alkoxy and C1-C 20 A macromolecular structure according to any one of embodiments 1 to 132, wherein each heteroalkyl is optionally substituted with one or more C1-C6 alkyl, oxo, halo, or hydroxyl groups. Embodiment 137. The mooring section has the following structure: [ka] [In the formula, Y is a C1-C6 alkyl, oxo, halo, or hydroxyl molecule, as needed. 20 It is heteroalkyl, p is an integer between 1 and 12. A macromolecular structure as described in Embodiment 135, represented by [the specified symbol]. Embodiment 138. The mooring section has the following structure: [ka] A macromolecular structure as represented by Embodiment 135 or 137. Embodiment 139. A macromolecular structure according to any one of Embodiments 1 to 137, wherein the macromolecular chain is a homopolymer. Embodiment 140. A macromolecular structure according to any one of Embodiments 1 to 137, wherein the macromolecular chain is a block copolymer. Embodiment 141. A macromolecular structure according to any one of Embodiments 1 to 137, wherein the macromolecular chain is a random copolymer. Embodiment 142. A macromolecular structure according to any one of Embodiments 1 to 137, wherein the macromolecular chain is not crosslinked. Embodiment 143. A macromolecular structure according to any one of Embodiments 1 to 142, wherein the macromolecular chain comprises about 1 to about 100 repeating units. Embodiment 144. A macromolecular structure according to any one of Embodiments 1 to 143, wherein the macromolecular chain comprises about 1 to about 50 repeating units. Embodiment 145. A macromolecular structure according to any one of Embodiments 1 to 144, wherein the macromolecular chain comprises a molecular weight of approximately 0.5 kDa to approximately 25 kDa. Embodiment 146. A macromolecular structure according to any one of Embodiments 1 to 145, wherein the macromolecular chain comprises a molecular weight of approximately 0.5 kDa to approximately 10 kDa. Embodiment 147. A macromolecular structure according to any one of Embodiments 1 to 146, wherein the second end of the macromolecular chain is not coupled to the surface. Embodiment 148. The surface has at least one anchoring site / 50nm 2 A macromolecular structure according to any one of embodiments 1 to 147, including anchoring sites at a density. Embodiment 149. The surface has approximately one anchoring site / 50nm 2 ~Approximately 1 mooring site / 5nm 2 A macromolecular structure according to any one of embodiments 1 to 148, including anchoring sites at a density. Embodiment 150. A method for producing a macromolecular structure according to any one of Embodiments 1 to 149, wherein the method is (a) the step of providing a surface; (b) The step of coupling a polymer initiator to the surface to form an initiator surface; and (c) The step of bringing the initiator surface into contact with the monomer described in any one of Embodiments 1 to 113 to form a macromolecular structure. Methods that include... Embodiment 151. The method according to Embodiment 150, wherein the surface contains particles. Embodiment 152. The method according to Embodiment 150 or 151, wherein the particles are nanoparticles or microparticles. Embodiment 153. The method according to any one of Embodiments 150 to 152, wherein the particles include a diameter of about 100 nm to about 500 nm. Embodiment 154. The method according to any one of Embodiments 150 to 153, wherein the particles include a diameter of about 100 nm to about 300 nm. Embodiment 155. The method according to any one of Embodiments 150 to 154, wherein the particles contain iron oxide. Embodiment 156. The method according to any one of Embodiments 150 to 155, wherein the particles have an iron oxide core. Embodiment 157. The method according to any one of Embodiments 150 to 156, wherein the particles are superparamagnetic iron oxide (nano) particles. Embodiment 158. The method according to any one of Embodiments 150 to 157, wherein the particles contain silicon dioxide. Embodiment 159. The method according to any one of Embodiments 150 to 158, wherein the particles have a core-shell structure. Embodiment 160. The method according to any one of Embodiments 150 to 159, wherein the particles comprise an iron oxide core having a silica shell. Embodiment 161. The method according to any one of Embodiments 150 to 160, wherein the surface is functionalized with an alkoxysilane. Embodiment 162. The method according to any one of Embodiments 150 to 161, wherein the surface is functionalized with aminopropyltetraethoxysilane (APTES). Embodiment 163. The method according to any one of Embodiments 150 to 162, wherein the coupling step includes the addition of a base. Embodiment 164. The method according to Embodiment 163, wherein the base comprises triethylamine. Embodiment 165. The method according to Embodiment 163 or 164, wherein the base is added at approximately 0°C. Embodiment 166. The method according to any one of Embodiments 150 to 165, wherein the coupling step includes a step of providing a polymer initiator to the surface at approximately 0°C. Embodiment 167. Polymer initiator has the following structure: [ka] [In the formula, X is a halogen; R 10 [is an initiator group] The method according to any one of embodiments 150 to 166, as represented by [the specified figure]. Embodiment 168. The method according to Embodiment 167, wherein the initiator group is a halogen. Embodiment 169. The method according to any one of Embodiments 150 to 168, wherein the contact step includes a temperature of at least 25°C. Embodiment 170. The method according to any one of Embodiments 150 to 169, wherein the contact step includes a temperature of about 25°C to about 75°C. Embodiment 171. The method according to any one of Embodiments 150 to 170, wherein the contact step includes bringing the initiator surface into contact with a mixture of monomers and an organic solvent. Embodiment 172. The method according to Embodiment 171, wherein the organic solvent is dimethylformamide. Embodiment 173. A method for producing a macromolecular structure according to any of Embodiments 1 to 149, wherein the method is (a) the step of providing a surface; (b) A step of coupling vinyl groups to the surface to form a vinyl-functionalized surface; (c) The vinyl-functionalized surface is brought into contact with a crosslinked monomer and a monomer selected from hydroxyalkyl methacrylate, aminoalkyl methacrylate, alkynyl methacrylate, glycidylalkyl methacrylate, hydroxyalkyl acrylate, aminoalkyl acrylate, alkynyl acrylate, or glycidylalkyl acrylate to form a coupled crosslinked polymer on the surface; (d) A step of coupling a polymer initiator to a crosslinked polymer to form an initiator surface; (e) The step of bringing the initiator surface into contact with the monomer described in any one of Embodiments 1 to 113 to form a macromolecular structure. Methods that include... Embodiment 174. The method according to Embodiment 173, wherein the surface contains particles. Embodiment 175. The method according to Embodiment 173 or 174, wherein the particles are nanoparticles or microparticles. Embodiment 176. The method according to any one of Embodiments 173 to 175, wherein the particles include a diameter of about 100 nm to about 500 nm. Embodiment 177. The method according to any one of Embodiments 173 to 176, wherein the particles include a diameter of about 100 nm to about 300 nm. Embodiment 178. The method according to any one of Embodiments 173 to 177, wherein the particles contain iron oxide. Embodiment 179. The method according to any one of Embodiments 173 to 178, wherein the particles have an iron oxide core. Embodiment 180. The method according to any one of Embodiments 173 to 179, wherein the particles are magnetic. Embodiment 181. The method according to any one of Embodiments 173 to 180, wherein the particles are superparamagnetic iron oxide (nano) particles. Embodiment 182. The method according to any one of Embodiments 173 to 181, wherein the particles have a core-shell structure. Embodiment 183. The method according to any one of Embodiments 173 to 182, wherein the particles comprise an iron oxide core having a silica shell. Embodiment 184. The method according to any one of Embodiments 173 to 183, wherein the vinyl-functionalized surface comprises a vinyl acrylate. Embodiment 185. The crosslinked monomer is [ka] [In the formula, R 1 , R 2 , R 3 , R 1’ , R 2’ , and R 3’ Each of these is independently selected from hydrogen or C1-C6 alkyl groups; Z is -O- or -NH; R 8 [These are C1-C6 alkyl, divalent metal, symmetric or asymmetric disulfide compounds.] The method according to any one of embodiments 173 to 184, including a structure represented by [the given method]. Embodiment 186. Polymer initiator has the following structure: [ka] [In the formula, X is a halogen; R 10 [is an initiator group] The method according to any one of embodiments 173 to 185, as represented by [the specified method]. Embodiment 187. The method according to Embodiment 186, wherein the initiator group is selected from halogens, epoxides, or double bonds. Embodiment 188. The method according to any one of Embodiments 173 to 187, wherein the contact step includes a temperature of at least 25°C. Embodiment 189. The method according to any one of Embodiments 173 to 188, wherein the contact step includes a temperature of about 25°C to about 75°C. Embodiment 190. The method according to any one of Embodiments 173 to 189, wherein the contact step includes bringing the initiator surface into contact with a mixture of monomers, crosslinked monomers, and an organic solvent. Embodiment 191. The method according to Embodiment 190, wherein the organic solvent is dimethylformamide. Embodiment 192. The method according to any one of Embodiments 173 to 191, wherein the contact step includes an inert condition. Embodiment 193. The method according to any one of Embodiments 173 to 192, wherein the coupling step includes an inert condition. Embodiment 194. A composition comprising a macromolecular structure described in any one of Embodiments 1 to 149, and biomolecules adsorbed to the macromolecular structure. Embodiment 195. The composition according to Embodiment 194, wherein biomolecules adsorbed to a macromolecular structure form a biomolecular corona on the macromolecular structure. Embodiment 196. The composition according to Embodiment 194 or 195, comprising a biological sample in contact with a macromolecular structure. Embodiment 197. The composition according to Embodiment 196, wherein the biological sample comprises plasma, serum, or blood. Embodiment 198. The composition according to Embodiment 196 or 197, wherein the biological sample comprises a plurality of proteins. Embodiment 199. The composition according to any one of Embodiments 194 to 198, wherein at least 100 different biomolecules are adsorbed onto a macromolecular structure. Embodiment 200. The composition according to any one of Embodiments 194 to 199, wherein approximately 100 to approximately 1000 different proteins are adsorbed onto a macromolecular structure. Embodiment 201. A composition according to any one of Embodiments 194 to 200, wherein the biomolecule comprises a protein. Embodiment 202. A method for identifying proteins in a sample, wherein the method is (a) Incubating one or more macromolecular structures described in any one of embodiments 1 to 113 with a biological sample containing biomolecules to form a biomolecular corona; (b) the step of isolating at least some of the biomolecules in the biomolecular corona; and (c) Steps for assaying the biomolecular coronavirus Methods that include... Embodiment 203. The method according to Embodiment 202, wherein the assay step can identify a group of 1 to 20,000 proteins. Embodiment 204. The method according to Embodiment 202 or 203, wherein the assay step can identify a group of 1,000 to 10,000 proteins. Embodiment 205. The method according to any one of Embodiments 202 to 204, wherein the assay step can identify a group of 1,000 to 5,000 proteins. Embodiment 206. The method according to any one of Embodiments 202 to 205, wherein the assay step can identify a group of 1,200 to 2,200 proteins. Embodiment 207. The method according to any one of Embodiments 202 to 206, wherein the protein group comprises a peptide sequence having a minimum length of 7 amino acid residues. Embodiment 208. The method according to any one of Embodiments 202 to 207, wherein the assay step can identify 1,000 to 10,000 proteins. Embodiment 209. The method according to any one of Embodiments 202 to 208, wherein the assay step can identify 1,800 to 5,000 proteins. Embodiment 210. The method according to any one of Embodiments 202 to 209, wherein the sample comprises multiple samples. Embodiment 211. The method according to any one of Embodiments 202 to 210, wherein the plurality of samples include at least two or more spatially separated samples. Embodiment 212. The method according to any one of Embodiments 211, wherein the incubation step includes bringing at least two or more spatially separated samples into contact with one or more macromolecular structures at the same time. Embodiment 213. The method according to Embodiment 211 or 212, wherein the isolation step includes magnetically isolating one or more macromolecular structures from unbound proteins in at least two or more spatially separated samples of a plurality of samples at the same time. Embodiment 214. The method according to any one of Embodiments 211 to 213, wherein the assay step includes assaying multiple distinct biomolecular coronas to identify proteins in at least two or more spatially separated samples at the same time. Embodiment 215. The method according to any one of Embodiments 202 to 214, further comprising repeating steps, wherein, when repeated, the incubation step, isolation step, and assay step result in a quantile normalization coefficient (QNCV) of 20% or less variation, determined by comparing the peptide mass spectrometry properties from at least three complete assay repeats for each macromolecular structure in one or more macromolecular structures. Embodiment 216. The method according to any one of Embodiments 202 to 215, wherein, when repeated, the incubation step, isolation step, and assay step result in a quantile normalization coefficient (QNCV) of 10% or less variation, determined by comparing the peptide mass spectrometry properties from at least three complete assay repeats for each macromolecular structure in one or more macromolecular structures. Embodiment 217. The method according to any one of Embodiments 202 to 216, wherein the assay step can identify proteins over a dynamic range of at least 6, at least 7, at least 8, at least 9, or at least 10. Embodiment 218. The method according to any one of Embodiments 202 to 217, further comprising the step of washing one or more macromolecular structures at least once or at least twice after isolating one or more macromolecular structures from an unbound protein. Embodiment 219. The method according to any one of Embodiments 202 to 218, further comprising the step of lysing proteins in a plurality of distinct biomolecules in corona after the assay step. Embodiment 220. The method according to any one of Embodiments 202 to 219, further comprising the step of digesting a plurality of distinct biomolecular proteins in corona to produce digested peptides. Embodiment 221. The method according to any one of Embodiments 202 to 220, further comprising the step of purifying the digested peptide. Embodiment 222. The method according to any one of Embodiments 202 to 221, wherein the assay step includes a step of identifying proteins in the sample using mass spectrometry. Embodiment 223. The method according to any one of Embodiments 202 to 222, wherein the assay step is performed over approximately 2 to 4 hours. Embodiment 224. The method according to any one of Embodiments 202 to 223, wherein the method is carried out over approximately 1 to approximately 20 hours. Embodiment 225. The method according to any one of Embodiments 202 to 224, wherein the method is carried out over approximately 2 to approximately 10 hours. Embodiment 226. The method according to any one of Embodiments 202 to 225, wherein the method is carried out over approximately 4 to 6 hours. Embodiment 227. The method according to any one of Embodiments 202 to 226, wherein the isolation step takes about 30 minutes or less, about 15 minutes or less, about 10 minutes or less, about 5 minutes or less, or about 2 minutes or less. Embodiment 228. The method according to any one of Embodiments 202 to 227, wherein the plurality of samples include at least 10 spatially separated samples, at least 50 spatially separated samples, at least 100 spatially separated samples, at least 150 spatially separated samples, at least 200 spatially separated samples, at least 250 spatially separated samples, or at least 300 spatially separated samples. Embodiment 229. The method according to any one of Embodiments 202 to 228, wherein the plurality of samples comprises at least 96 samples. Embodiment 230. The method according to any one of Embodiments 202 to 229, wherein one or more macromolecular structures include at least two distinct macromolecular structures, at least three distinct macromolecular structures, at least four distinct macromolecular structures, at least five distinct macromolecular structures, at least six distinct macromolecular structures, at least seven distinct macromolecular structures, at least eight distinct macromolecular structures, at least nine distinct macromolecular structures, at least ten distinct macromolecular structures, at least eleven distinct macromolecular structures, at least twelve distinct macromolecular structures, at least thirteen distinct macromolecular structures, at least fourteen distinct macromolecular structures, at least fifteen distinct macromolecular structures, at least twenty distinct macromolecular structures, at least twenty-five distinct macromolecular structures, or at least thirty distinct macromolecular structures. Embodiment 231. The method according to any one of Embodiments 202 to 230, wherein one or more macromolecular structures comprise at least 10 distinct macromolecular structures. Embodiment 232. The method according to any one of Embodiments 211 to 231, wherein at least two spatially separated samples differ by at least one physicochemical property. Embodiment 233. The method according to any one of Embodiments 202 to 232, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure share at least one physicochemical property and differ by at least one physicochemical property, and as a result the first distinct macromolecular structure and the second distinct macromolecular structure are different. Embodiment 234. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure share at least two physicochemical properties and differ by at least two physicochemical properties, and as a result the first distinct macromolecular structure and the second distinct macromolecular structure are different. Embodiment 235. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure share at least one physicochemical property and differ by at least two physicochemical properties, as a result the first distinct macromolecular structure and the second distinct macromolecular structure are different. Embodiment 236. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure share at least two physicochemical properties and differ by at least one physicochemical property, and as a result the first distinct macromolecular structure and the second distinct macromolecular structure are different. Embodiment 237. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure comprise a carboxylate material, the first distinct particle is a microparticle, and the second distinct macromolecular structure is a nanoparticle. Embodiment 238. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure comprise a surface charge of 0 mV to -50 mV, the first distinct macromolecular structure has a diameter of less than 200 nm, and the second distinct macromolecular structure has a diameter of more than 200 nm. Embodiment 239. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure comprise a diameter of 100 to 400 nm, the first distinct macromolecular structure has a positive surface charge, and the second distinct macromolecular structure has a neutral surface charge. Embodiment 240. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure are nanoparticles, the first distinct macromolecular structure has a surface charge of less than -20 mV, and the second distinct macromolecular structure has a surface charge of greater than -20 mV. Embodiment 241. The method according to any one of Embodiments 202 to 233, wherein one or more macromolecular structures comprise a first distinct macromolecular structure and a second distinct macromolecular structure, the first distinct macromolecular structure and the second distinct macromolecular structure are microparticles, the first distinct macromolecular structure has a negative surface charge, and the second distinct macromolecular structure has a positive surface charge. Embodiment 242. The method according to any one of Embodiments 202 to 241, wherein one or more macromolecular structures comprise a subset of negatively charged nanoparticles, each particle of the subset differing by at least one surface chemical group. Embodiment 243. The method according to any one of Embodiments 202 to 242, wherein one or more macromolecular structures comprise a first distinct macromolecular structure, a second particle, and a third distinct macromolecular structure, the first distinct macromolecular structure, the second distinct macromolecular structure, and the third distinct macromolecular structure comprise an iron oxide core, a polymer shell, and have a diameter of less than about 500 nm, the first distinct macromolecular structure comprises a negative charge, the second distinct macromolecular structure comprises a positive charge, the third distinct macromolecular structure comprises a neutral charge, and the diameter is the average diameter measured by dynamic light scattering. Embodiment 244. The method according to any one of Embodiments 202 to 243, wherein at least one distinct macromolecular structure of one or more macromolecular structures is a nanoparticle. Embodiment 245. The method according to any one of Embodiments 202 to 244, wherein at least one distinct macromolecular structure of one or more macromolecular structures is a microparticle. Embodiment 246. The method according to any one of Embodiments 202 to 245, wherein at least one distinct macromolecular structure of one or more macromolecular structures is a superparamagnetic iron oxide particle. Embodiment 247. The method according to any one of Embodiments 202 to 246, wherein each particle of one or more macromolecular structures comprises an iron oxide material. Embodiment 248. The method according to any one of Embodiments 202 to 247, wherein at least one distinct macromolecular structure of one or more macromolecular structures has an iron oxide core. Embodiment 249. The method according to any one of Embodiments 202 to 248, wherein at least one distinct macromolecular structure of one or more macromolecular structures has iron oxide crystals embedded in a polystyrene core. Embodiment 250. The method according to any one of Embodiments 202 to 249, wherein each distinct macromolecular structure of one or more macromolecular structures is a superparamagnetic iron oxide particle. Embodiment 251. The method according to any one of Embodiments 202 to 250, wherein each of the one or more distinct macromolecular structures comprises an iron oxide core. Embodiment 252. The method according to any one of Embodiments 202 to 251, wherein each of the one or more macromolecular structures has an iron oxide crystal embedded in a polystyrene core. Embodiment 253. The method according to any one of Embodiments 202 to 252, wherein at least one distinct macromolecular structure of one or more macromolecular structures comprises a carboxylated polymer, an amination polymer, a zwitterionic polymer, or any combination thereof. Embodiment 254. The method according to any one of Embodiments 202 to 253, wherein at least one of the macromolecular structures comprises an iron oxide core having a silica shell coating. Embodiment 255. The method according to any one of Embodiments 202 to 254, wherein at least one distinct macromolecular structure of one or more macromolecular structures includes a negative surface charge. Embodiment 256. The method according to any one of Embodiments 202 to 255, wherein at least one distinct macromolecular structure of one or more macromolecular structures includes a positive surface charge. Embodiment 257. The method according to any one of Embodiments 202 to 256, wherein at least one distinct macromolecular structure of one or more macromolecular structures includes a neutral surface charge. Embodiment 258. A kit for identifying molecules in a biological sample, comprising one or more macromolecular structures described in Embodiments 1 to 113. Embodiment 259. The kit according to Embodiment 258, wherein the kit further comprises a solvent. Embodiment 260. The kit according to Embodiment 258 or 259, wherein the kit further comprises a digestive agent. Embodiment 261. The kit according to any one of Embodiments 258 to 260, wherein the kit further comprises a cleaning agent. Embodiment 262. The kit according to any one of Embodiments 258 to 261, wherein the kit further comprises an elution buffer. Embodiment 263. The kit according to any one of Embodiments 258 to 262, wherein the kit further includes a solid support for solid-phase extraction. Embodiment 264. The kit according to any one of Embodiments 258 to 263, wherein the kit further comprises a multiwell plate. Embodiment 265. The kit according to any one of Embodiments 258 to 264, wherein the kit further comprises a diluent. Embodiment 266. A system for identifying biomolecules in a biological sample, wherein the system is (a) A macromolecular structure according to any one of embodiments 1 to 113; (b) Suspension solution; (c) A biological sample containing a certain concentration of protein; and (d) An automated system comprising a network of distinct functional units for isolating biomolecules adsorbed to macromolecular structures, which is programmed to perform a series of steps. A system that includes this. Embodiment 267. The network of the unit is (a) A first unit including a multi-channel fluid transfer device for moving fluid between units within the system; (b) A second unit including support for storing multiple biological samples; (c) A third unit including a support for a sensor array plate having a compartment containing macromolecular structures for binding interactions with a population of analytes derived from a biological sample; (d) A fourth unit including support for storing multiple reagents; (e) A fifth unit including support for storing discarded reagents; and (f) A sixth unit including support for storing consumables used by multi-channel fluid transfer equipment. The system according to embodiment 266, including the system described above. Embodiment 268. A series of steps, (a) The step of bringing a biological sample into contact with a designated section of the sensor array; (b) Incubating the biological sample with macromolecular structures contained within a compartment of the sensor array plate; (c) the step of removing the supernatant from the sensor array plate; and (d) Step of preparing biomolecules adsorbed onto macromolecular structures for mass spectrometry. The system according to embodiment 266 or 267, including the system described in embodiment 266 or 267. Embodiment 269. The system according to any one of Embodiments 266 to 268, wherein i. to iii. are incubated at a temperature of approximately 20 degrees Celsius to approximately 80 degrees Celsius. Embodiment 270. The system according to any one of Embodiments 266 to 269, wherein the suspension solution comprises Tris EDTA 150 mM KCl and 0.05% CHAPS buffer. Embodiment 271. The system according to any one of Embodiments 266 to 270, wherein the suspension solution comprises 10 mM Tris HCl pH 7.4 and 1 mM EDTA.

[0313] Preferred embodiments of the Disclosure are shown and described herein, but it will be obvious to those skilled in the art that such embodiments are provided only as examples. Numerous variations, changes, and substitutions will be recalled herein without departing from the Disclosure. It should be understood that various alternatives to the embodiments of the Disclosure described herein may be used in the practice of the Disclosure. The following claims define the scope of the Disclosure, and methods and structures within the scope of these claims, as well as their equivalents, are intended to be encompassed thereby. [Examples]

[0314] (Example 1) Synthesis of SPION@SiO2-APTES [ka] Silica-coated superparamagnetic iron oxide nanoparticles (SPION@SiO2) were suspended in DMF and sonicated for 15 minutes. The nanoparticle solution was purged with N2 gas for 20 minutes, and the particle solution was heated at 120°C for 4 hours. After cooling, SPION@SiO2 was washed three times with DMF and then isolated. The isolated particles were dispersed in N,N-dimethylacetamide (DMAc) (2 L). 4.50 g of (3-aminopropyltriethoxysilane) (APTES) was added to the solution, and the resulting solution was reacted at 120°C for 4 hours to obtain the SPION@SiO2-APTES product. (Example 2) Synthesis of SPION@SiO2-APTES-Br [ka]

[0315] SPION@SiO2-APTES in DMF was washed twice with tetrahydrofuran (THF), and then resuspended in THF (801 mL) for 15 minutes under sonication. Triethylamine (10.40 g) was added under N2 conditions in an ice bath (0°C). After the addition of triethylamine, 2-bromoisobutyryl bromide (2.509 g) was added dropwise at 0°C. The reaction was stirred overnight at room temperature (16 hours). The resulting material was washed once with THF, once with ethanol, once with water, and then once with THF. The final product was dried over N2. (Example 3) Synthesis of compound 2, SPION@SiO2-SIP-POEGMA [ka]

[0316] Initiator particles SPION@SiO2-APTES-Br (1.000 g), CuBr2 (0.010 g), N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) (0.240 g), monomer oligo(ethylene glycol) methyl ether methacrylate (OEGMA, MW500) (5.000 g), and 25 mL of dimethylformamide (DMF) were added to a three-necked flask. The mixture was sonicated for 15 minutes and purged with N2 for a further 15 minutes. Separately, 0.500 g of L-ascorbic acid was dissolved in 10 mL of DMF and purged with N2 for at least 15 minutes. The mixture containing the monomer and nanoparticle suspension was heated to 35°C under N2, and the L-ascorbic acid solution was added at a rate of 0.05 mL / min via a syringe pump. The reaction mixture was maintained at 35°C for 16 hours to obtain compound 2. (Example 4) Characterization of macromolecular structures

[0317] Compounds 1-3 were synthesized according to the synthesis described in Examples 1-3 and variations of the scheme shown in Figure 1. An exemplary synthesis scheme for compound 1 is shown in Figure 4. An exemplary synthesis scheme for compound 2 is shown in Figure 5. An exemplary synthesis scheme for compound 3 is shown in Figure 6. Particle size was characterized by DLS, surface charge by zeta potential, and macromolecular chain % by TGA (weight loss %). Particle size was compared with the particle size before functionalization with macromolecular chains. The obtained data can be found in Table 4. [Table 4]

[0318] Compounds 5, 6, and 7 were also synthesized using the general procedure of Examples 1-3. Compounds 1, 2, 5, 6, and 7 were analyzed for organic matter percentage by thermogravimetric analysis. The results are shown in Table 5. The organic matter percentage in the particles ranged from 9.14% to 15.88%, which was higher than the organic matter percentage found on the initiator surface before further functionalization. [Table 5-1] [Table 5-2]

[0319] Scanning electron microscope (SEM) images of compounds 2, 5, 6, and 7 are shown in Figure 3A. Compound 5 has a size of 296 nm as measured by SEM, compound 6 has a size of 230 nm as measured by SEM, compound 2 has a size of 311 nm as measured by SEM, and compound 7 has a size of 302 nm as measured by SEM. Figure 3B shows a transmission electron microscope image of compound 2, highlighting the polymer brush formed on the surface of the particle.

Claims

1. It is a macromolecular structure, (I) Surface; (II) Mooring portion coupled to the surface; and (III) Macromolecule chain The macromolecular chain includes, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain is 【Transformation 73】 [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH-; Q is -CH ２ - or ethylene glycol; A is structure: 【Chemistry 74】 A polymer side chain containing repeating units derived from a monomer represented by; m is an integer selected from 1 to 20; 【Chemistry 75】 It is either a single bond or a double bond; R １ , R ２ , R １’ , R ２’ , and R ３’ Each of them independently consists of hydrogen or -C １ ~C ６ Selected from alkyl groups; R ３ is hydrogen, C １ to C ６ alkyl, or a 3-, 5- or 6-membered heterocyclic ring optionally substituted with one or more C １ to C ６ alkyl; R ４ is absent, hydrogen, sulfonate, carboxylate, C １ ~C ４ C as needed, substituted with alkylene, amine, quaternary ammonium cation, or halogen １ ~C ６ It is alkyl; R ５ is hydrogen, C １ ~C ６ Alkyl, C substituted with one or more hydroxyls １ ~C ８ Alkyl, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle, or C, optionally substituted with alkyl or oxo groups. １ ~C ｎ１ C may be further substituted as needed with ethylene glycol, amine, hydroxyl, aryl, or sulfonate. １ ~C ８ Alkylamines, C as needed, substituted with one or more oxo or halogens １ ~C ８ Alkoxy, one or more pyrenes, two or more fused 5- or 6-membered rings, optionally substituted benzyl, trimethoxysilane, or phosphorocline-substituted C １ ~C ３ Alkyl, C １ ~C １２ Alkylamine, or C １ ~C ４ It is alkylene; R ６ is hydrogen or C １ ~C ６ It is alkyl, R ７ is hydrogen, C １ ~C ６ Alkyl, C substituted with one or more hydroxyls １ ~C ８ Alkyl, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle, or C, optionally substituted with alkyl or oxo groups. １ ~C ｎ１ C, which may be further substituted as needed with ethylene glycol, amine, or sulfonate. １ ~C ８ Alkylamines, C as needed, substituted with one or more oxo or halogens １ ~C ８ Alkoxy, one or more pyrenes, two or more fused 5- or 6-membered rings, optionally substituted benzyl, trimethoxysilane, or phosphorocline-substituted C １ ~C ３ Alkyl, or C １ ~C ４ It is alkylene; R ８ C １ ~C ６ Alkyl, divalent metal, or symmetric or asymmetric disulfide; R ９ is hydrogen or oxo; n １ [This is an integer selected from 1 to 100.] A macromolecular structure comprising two or more distinct repeating units derived from monomers represented by a structure selected from the group consisting of the following.

2. R ３ However, the macromolecular structure according to claim 1 is methyl.

3. R ５ However, C １ ~C ｎ１ The macromolecular structure according to claim 2, wherein the macromolecular structure is ethylene glycol.

4. It is a macromolecular structure, (I) Surface; (II) Mooring portion coupled to the surface; and (III) Macromolecule chain The macromolecular chain includes, and the first end of the macromolecular chain is covalently bonded to the anchoring site, and the macromolecular chain is 【Transformation 76】 [In the formula, each of X and Y is independently -C-, -O-, or -N-; Each Z is independently -O- or -NH; Q is -CH ２ - or ethylene glycol; A is structure: 【Chemical 77】 A polymer side chain containing repeating units derived from a monomer represented by; m is between 1 and 6; R １ , R ２ , R １’ , R ２’ , and R ３’ Each of them independently contains hydrogen or C １ ~C ６ Selected from alkyl groups; R ３ is hydrogen, C １ ~C ６ Alkyl, or one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle optionally substituted with alkyl groups; R ４ C is absent, hydrogen, and substituted as needed with halogens. １ ~C ６ Alkyl, C １ ~C ４ Alkylene, C １ ~C ６ It is an alkyl, sulfonate, amine, quaternary ammonium cation, or carboxylate; R ５ is hydrogen, C １ -C ６ alkyl, C １ -C ８ alkyl substituted with one or more hydroxyls, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, a 3-, 5- or 6-membered heterocycle optionally substituted with one or more C １ -C ６ alkyl or oxo, or C １ -C ｎ１ ethylene glycol, amine, hydroxyl, aryl, or sulfonate further substituted C １ -C ８ alkylamine, a C １ -C ８ alkoxy optionally substituted with one or more pyrenes, two or more fused 5- to 6-membered rings optionally further substituted (e.g., with two or more fused 6-membered rings optionally further substituted), benzyl optionally substituted, trimethoxysilane, or -C １ -C ３ alkyl, C １ -C １２ alkylamine, or C １ -C ４ alkylene; R ６ is hydrogen or linear C １ ~C ６ It is alkyl, R ７ is hydrogen, C １ ~C ６ Alkyl, C substituted with one or more hydroxyls １ ~C ８ Alkyl, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle, or C, optionally substituted with alkyl or oxo groups. １ ~C ｎ１ C further substituted with ethylene glycol, amine, or sulfonate １ ~C ８ Alkylamines, C as needed, substituted with one or more oxo or halogens １ ~C ８ Alkoxy, one or more pyrene, two or more fused 5- or 6-membered rings as further substituted as needed (e.g., two or more fused 6-membered rings as further substituted as needed), as substituted benzyl, trimethoxysilane, or phosphorocoline as substituted as needed -C １ ~C ３ Alkyl, or C １ ~C ４ It is alkylene; R ８ C １ ~C ６ Alkyl, or symmetric or asymmetric disulfide; R ９ is hydrogen or oxo; n １ is an integer selected from 1 to 100; However, R ３ ga CH ３ If R ４ CH ３ is, or R ５ C is substituted with hydroxyl １ ~C ８ If it is alkyl, C １ ~C ８ [Further substitutions have been made.] A macromolecular structure containing repeating units derived from monomers, represented by a structure selected from the group consisting of the following.

5. It is a macromolecular structure, A macromolecular structure comprising (I) a surface and (II) a macromolecular chain coupled to the surface, wherein the macromolecular chain contains repeating units of formula (I): 【Transformation 78】 [In the formula, R １’’ , R ２’’ , and R ３’’ Each of them independently contains hydrogen or C １ ~C ６ It is alkyl; L is the linker part; A is, 【Transformation 79】 A polymer side chain comprising repeating units derived from monomers represented by a structure selected from the group consisting of; Each of X and Y is independently -C-, -O-, or -N-; Z is -O- or -NH; R １ , R ２ , R １’ , R ２’ , and R ３’ Each of them independently contains hydrogen or C １ ~C ６ Selected from alkyl groups; R ３ is hydrogen, C １ ~C ６ Alkyl, or one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle optionally substituted with alkyl groups; R ４ is absent, hydrogen, sulfonate, carboxylate, C １ ~C ４ C as needed, substituted with alkylene, amine, quaternary ammonium cation, or halogen １ ~C ６ It is alkyl; R ５ is hydrogen, C １ ~C ６ Alkyl, C substituted with one or more hydroxyls １ ~C ８ Alkyl, amine, azide, sulfonate, carbamate ester, asymmetric disulfide, one or more C １ ~C ６ A 3, 5, or 6-membered heterocycle, or C, optionally substituted with alkyl or oxo groups. １ ~C ｎ１ C further substituted with ethylene glycol, amine, hydroxyl, aryl, or sulfonate １ ~C ８ Alkylamines, C as needed, substituted with one or more oxo or halogens １ ~C ８ Alkoxy, one or more pyrene, two or more fused 5- or 6-membered rings, optionally substituted (e.g., two or more fused 6-membered rings, optionally substituted), optionally substituted benzyl, trimethoxysilane, or phosphorocoline-substituted C １ ~C ３ Alkyl, C １ ~C １２ Alkylamine, or C １ ~C ４ It is alkylene; R ６ is hydrogen or linear C １ ~C ６ It is alkyl, R ７ is hydrogen, C １ ~C ６ Alkyl, one or more C １ ~C ６ 3, 5, or 6-membered heterocycles optionally substituted with alkyl or oxo, substituted benzenes, hydroxyl-substituted C １ ~C ６ Alkyl, optionally substituted C １ ~C ８ It is an alkyl sulfonate; R ８ C １ ~C ６ Alkyl, divalent metal, or symmetric or asymmetric disulfide; R ９ is hydrogen or oxo; n １ is an integer selected from 1 to 100; n is an integer selected from 1 to 10,000.

6. The aforementioned large molecular chain has the following structure: 【Chemistry 80】 A macromolecular structure according to any one of claims 1 to 5, comprising the repeating unit derived from a monomer represented by

7. The macromolecular structure according to any one of claims 1 to 6, wherein the macromolecular chain includes the repeating unit derived from the monomer represented by the structure in Table 1.

8. The macromolecular structure according to any one of claims 1 to 7, wherein the macromolecular chain includes the repeating units derived from monomers represented by the structure in Table 2.

9. The aforementioned macromolecular structure 【Chemistry 81】 A macromolecular structure according to any one of claims 1 to 8, having a structure represented by [the given formula].

10. A method for producing a macromolecular structure according to any one of claims 1 to 9, wherein the method is (a) the step of providing a surface; (b) The step of coupling a polymer initiator to the surface to form an initiator surface; and (c) The step of bringing the initiator surface into contact with the monomer described in any one of claims 7 to 8 to form the macromolecular structure. Methods that include...

11. The method according to claim 10, wherein the surface contains particles.

12. The method according to claim 11, wherein the particles include a diameter of about 100 nm to about 500 nm.

13. A method for producing a macromolecular structure according to any one of claims 1 to 9, wherein the method is (a) the step of providing a surface; (b) A step of coupling vinyl groups to the surface to form a vinyl functionalized surface; (c) Contacting the vinyl-functionalized surface with a crosslinked monomer and a monomer selected from hydroxyalkyl methacrylate, aminoalkyl methacrylate, alkynyl methacrylate, glycidylalkyl methacrylate, hydroxyalkyl acrylate, aminoalkyl acrylate, alkynyl acrylate, or glycidylalkyl acrylate to form a crosslinked polymer coupled to the surface; (d) The step of coupling a polymer initiator to the crosslinked polymer to form an initiator surface; and (e) The step of bringing the initiator surface into contact with the monomer according to any one of claims 7 to 8 to form the macromolecular structure. Methods that include...

14. The polymer initiator has the following structure: 【Chemistry 82】 [In the formula, X is a halogen; R １０ [This is the initiator group.] The method according to claim 13, as represented by [the specified method].

15. A composition comprising a macromolecular structure according to any one of claims 1 to 14, and a biomolecule adsorbed onto the macromolecular structure.

16. The composition according to claim 15, wherein at least 100 different biomolecules are adsorbed onto the macromolecular structure.

17. A method for identifying proteins in a sample, wherein the method is (a) Incubating one or more macromolecular structures according to any one of claims 1 to 9 with a biological sample containing biomolecules to form a biomolecular corona; (b) the step of isolating at least a portion of the biomolecules in the biomolecular corona; and (c) Step of assaying the biomolecular coronavirus. Methods that include...

18. The method according to claim 17, wherein the assay step can identify 1 to 20,000 protein groups.

19. A kit for identifying molecules in a biological sample, wherein the kit comprises one or more macromolecular structures as described in any one of claims 1 to 9.

20. A system for identifying biomolecules in a biological sample, wherein the system is (a) The macromolecular structure according to any one of claims 1 to 9; (b) Suspension solution; (c) A biological sample containing a certain concentration of protein; and (d) An automated system comprising a network of distinct functional units for isolating biomolecules adsorbed to the macromolecular structure, wherein the automated system is programmed to perform a series of steps. A system that includes this.

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