Nitrilotriacetic acid linkers, solid phase synthesis of nitrilotriacetic acid linkers and applications thereof

A surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR) sensor, the sensor comprising:

• (a) a substrate, wherein the substrate comprises a solid support coated with a metal layer;
• and
• (b) a nitrilotriacetic acid (NTA) linker having the formula:
• wherein the AA group comprises a linear or branched natural or synthetic amino acid group comprising one or more amino acids;
• the optional spacer comprises a linear or branched carbon chain, comprising one or more amino acids, a polymeric moiety, or any combination thereof, wherein in the absence of the spacer, the AA group is coupled to the one or more nitrilotriacetic acid (NTA) groups;
• the nitrilotriacetic acid (NTA) group comprises one or more nitrilotriacetic acid functional groups;
• wherein R is H, a short chain alkyl, or an NTA group;
• wherein n is the number of spacers in the linker;
• wherein o is the number of NTA groups in the linker;
• wherein p is the number of
• moieties;
• (c) wherein the AA group of the NTA linker is coupled to the metal layer;
• and
• (d) wherein the one or more nitrilotriacetic acid functional groups of the linker are capable of binding to one or more ligands and/or analytes.

A method for detection of an analyte in a fluid using a surface plasmon resonance (SPR or LSPR) sensor, comprising:

• providing an SPR or LSPR sensor comprising a surface, the surface comprising a solid support coated with a metal layer and having a nitrilotriacetic acid linker attached to the metal layer, the nitrilotriacetic acid linker having the formula:
• wherein the AA group comprises a linear or branched natural or synthetic amino acid group comprising one or more amino acids;
• the optional spacer comprises a linear or branched carbon chain, comprising one or more amino acids, a polymeric moiety, or any combination thereof, wherein in the absence of the spacer, the AA group is coupled to the one or more nitrilotriacetic acid (NTA) groups;
• the nitrilotriacetic acid (NTA) group comprises one or more nitrilotriacetic acid functional groups;
• wherein R is H, a short chain alkyl, or an NTA group;
• wherein n is the number of spacers in the linker;
• wherein o is the number of NTA groups in the linker;
• wherein p is the number of
• moieties;
• and
• optionally one or more ligands coupled to the nitrilotriacetic acid linker;
• contacting a fluid comprising an analyte with the SPR or LSPR sensor;
• and
• measuring an optical signal to detect a change in the optical signal in response to the contacting to measure the analyte in the fluid