Affinity encoded oscillator arrays, methods, and related aspects for measuring molecular binding kinetics

A method of performing multiplex detection of ligand binding kinetics, the method comprising:

• (a) contacting a first ligand with an array of nucleic acid barcoded oscillators disposed on a first surface of a substrate that comprises an electrically conductive coating, wherein the nucleic acid barcoded oscillators each comprise a nanoparticle attached to the first surface via one or more linker moieties, wherein at least a first nucleic acid barcoded oscillator comprises one or more first ligand binding moieties and one or more first barcode coding nucleic acids attached to the nanoparticle of the first nucleic acid barcoded oscillator, wherein at least a second nucleic acid barcoded oscillator comprises one or more second ligand binding moieties and one or more second barcode coding nucleic acids attached to the nanoparticle of the second nucleic acid barcoded oscillator, wherein the first ligand binding moieties differ from the second ligand binding moieties, wherein the first barcode coding nucleic acids differ from the second barcode coding nucleic acids, and wherein the first ligand is contacted with the array of nucleic acid barcoded oscillators under conditions sufficient for the first ligand to at least partially bind to the first and/or second ligand binding moieties;
• (b) applying an alternating current electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate;
• (c) detecting changes, if any, in oscillation amplitudes of at least the first and second nucleic acid barcoded oscillators over a duration to produce a first set of ligand binding data;
• (d) replacing the first ligand from the array of nucleic acid barcoded oscillators with buffer;
• (e) repeating steps (a)-(c) using a second ligand that differs from the first ligand to produce a second set of ligand binding data, wherein the second ligand is contacted with the array of nucleic acid barcoded oscillators under conditions sufficient for the second ligand to at least partially bind to the first and/or second ligand binding moieties;
• (f) contacting one or more first barcode decoding nucleic acids with the array of nucleic acid barcoded oscillators disposed on the first surface of the substrate, wherein the first barcode decoding nucleic acids are at least partially complementary to the first and/or second barcode coding nucleic acids, and wherein the first barcode decoding nucleic acids are contacted with the array of nucleic acid barcoded oscillators under conditions sufficient for the first barcode decoding nucleic acids to at least partially hybridize with the first and/or second barcode coding nucleic acids;
• (g) applying the alternating current electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate;
• (h) detecting changes, if any, in oscillation amplitudes of at least the first and second nucleic acid barcoded oscillators over a duration to produce a first set of barcode decoding data;
• (i) replacing the first barcode decoding nucleic acids from the array of nucleic acid barcoded oscillators with buffer;
• detecting changes, if any, in oscillation amplitudes of at least the first and second nucleic acid barcoded oscillators over a duration to produce a first set of ligand binding data;
• (j) repeating steps (f)-(h) using one or more second barcode decoding nucleic acids to produce a second set of barcode decoding data, wherein the second barcode decoding nucleic acids are at least partially complementary to the first and/or second barcode coding nucleic acids, wherein the second barcode decoding nucleic acids differ from the first barcode decoding nucleic acids, and wherein the second barcode decoding nucleic acids are contacted with the array of nucleic acid barcoded oscillators under conditions sufficient for the second barcode decoding nucleic acids to at least partially hybridize with the first and/or second barcode coding nucleic acids, thereby performing the multiplex detection of the ligand binding kinetics.