Microprobe-capture in-emitter elution-electrospray ionization

Inventor: Ruben Yiqi Luo (Redwood City, CA)

Assignee: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

G01N33/6851 H01J49/165

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Quick Facts

Patent No.: US 12669509
App. No.: 18/126,891
Granted: Jun 30, 2026
Kind: B2

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Abstract

Provided herein is a method for analyzing a molecular interaction. In some embodiments the method may comprise: capturing an analyte on a probe that comprises a binding agent, inserting the probe into the interior capillary of an electrospray emitter, releasing the analyte from the probe while it is in the emitter using an elution liquid, nebulizing the analyte by electrospray; and analyzing the nebulized analyte by mass spectrometry.

Claims (26)

1 . A method for analyzing a molecular interaction, comprising:

(a) capturing an analyte on a quartz glass thin-film interferometry (TFI) probe that comprises a binding agent at one end of the probe;

(b) inserting the entire probe into the interior capillary of an electrospray emitter that has a tip, wherein the inserting places the end of the probe that has the binding agent and analyte adjacent to the tip;

(d) nebulizing the analyte by electrospray from the tip of the electrospray emitter; and

(e) analyzing the nebulized analyte by mass spectrometry.

2 . The method of claim 1 , further comprising detecting binding of the analyte by the binding agent by thin-film interferometry.

3 . The method of claim 1 , further comprising measuring the kinetics of binding of the analyte to the binding agent by thin-film interferometry.

4 . The method of claim 1 , wherein the elution liquid comprises a solvent.

5 . The method of claim 1 , wherein the releasing and nebulizing are done in the presence of a sheath fluid.

6 . The method of claim 1 , wherein the mass spectrometry is a high-resolution mass spectrometry.

7 . The method of claim 6 , wherein the analyzing of (e) is done by a time of flight (TOF), Orbitrap or FT-ICR mass spectrometer.

8 . The method of claim 1 , wherein the method comprises, prior to step (b):

dipping the probe into a sample that comprises analytes;

washing the probe to remove unbound analytes; and

detecting binding of analytes to the probe by thin-film interferometry.

9 . The method of claim 1 , wherein the elution liquid is delivered by a capillary that is operably connected to capillary of the emitter.

10 . The method of claim 1 , wherein the binding agent is an antibody.

11 . The method of claim 1 , wherein the binding agent is an antibody and the analyte comprises one or more epitopes for the antibody.

12 . The method of claim 1 , wherein the binding agent is MHC protein.

13 . The method of claim 12 , wherein the analyte comprises one or more peptide fragments.

14 . An apparatus comprising:

an electrospray emitter having a tip and an interior capillary; and a quartz thin-film interferometry (TFI) probe comprising a binding agent thereon at one end of the probe; wherein the thin-film interferometry (TFI) probe is configured to fit entirely into the interior capillary of the electrospray emitter.

15 . The apparatus of claim 14 , wherein the emitter is operably connected to a reservoir of elution liquid.

16 . The apparatus of claim 14 , wherein the apparatus further comprises a mass spectrometer.

17 . The apparatus of claim 14 , wherein the apparatus further comprises a spectrophotometer.