A method of making higher order multi-ligand capture agents, the method comprising: (i) contacting a modified anchor ligand with a first plurality of candidate ligands and a target, whereby the modified anchor ligand is covalently linked to one or more of the candidate ligands in a reaction catalyzed by the target, thereby forming one or more bi-ligand capture agents, wherein each of the bi-ligand capture agents comprises the modified anchor ligand and one of the candidate ligands, wherein the anchor ligand binds the target, wherein the modified anchor ligand comprises a first functional group, wherein the first functional group is capable of specifically reacting with a corresponding second functional group, wherein each of the candidate ligands comprises the second functional group; (ii) modifying one of the bi-ligand capture agents to comprise a third functional group, wherein the third functional group is capable of specifically reacting with a corresponding fourth functional group, and (iii) contacting the modified bi-ligand capture agent with a second plurality of candidate ligands and a target, wherein the modified bi-ligand capture agent is covalently linked to one or more of the candidate ligands in a reaction catalyzed by the target, thereby forming one or more higher order multi-ligand capture agents, wherein each of the higher-order multi-ligand capture agents comprises the modified bi-ligand capture agent and one of the candidate ligands, wherein each of the candidate ligands in the second plurality of capture ligands comprises the fourth functional group; and wherein the dissociation constant for binding of the higher-order multi-ligand capture agent to the target is smaller than the dissociation constant for binding of the bi-ligand capture agent to the target, and the dissociation constant for binding of the bi-ligand capture agent to the target is smaller than the dissociation constant for binding of the modified anchor ligand to the target. (i) contacting a modified anchor ligand with a first plurality of candidate ligands and a target, whereby the modified anchor ligand is covalently linked to one or more of the candidate ligands in a reaction catalyzed by the target, thereby forming one or more bi-ligand capture agents, wherein each of the bi-ligand capture agents comprises the modified anchor ligand and one of the candidate ligands, wherein the anchor ligand binds the target, wherein the modified anchor ligand comprises a first functional group, wherein the first functional group is capable of specifically reacting with a corresponding second functional group, wherein each of the candidate ligands comprises the second functional group; (ii) modifying one of the bi-ligand capture agents to comprise a third functional group, wherein the third functional group is capable of specifically reacting with a corresponding fourth functional group, and (iii) contacting the modified bi-ligand capture agent with a second plurality of candidate ligands and a target, wherein the modified bi-ligand capture agent is covalently linked to one or more of the candidate ligands in a reaction catalyzed by the target, thereby forming one or more higher order multi-ligand capture agents, wherein each of the higher-order multi-ligand capture agents comprises the modified bi-ligand capture agent and one of the candidate ligands, wherein each of the candidate ligands in the second plurality of capture ligands comprises the fourth functional group; and