Method and device for detecting analytes

• US 9,921,163 B2
• Filed: 02/13/2014
• Issued: 03/20/2018
• Est. Priority Date: 02/15/2013
• Status: Active Grant

• Current Assignee: IMEC International, Panasonic Corporation (Panasonic Holdings Corporation)
• Original Assignee: IMEC International, Panasonic Corporation (Panasonic Holdings Corporation)
• Inventors: Jans, Hilde, Shioi, Masahiko, Jans, Karolien, Lagae, Liesbet
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): PERREIRA, MELISSA JEAN
• Application Number:
  US14/180,100
• Publication Number:
  US 20140234219A1
• Time in Patent Office: 1,496 Days
• Field of Search: 424 91
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/658 enhancement Raman, e.g. surface plasmons

Abstract

A method (200) for determining a concentration of an analyte in a fluid or fluid sample, comprises: providing (201) a SERS substrate comprising receptor molecules (107) capable of binding competitor molecules (106); contacting (202) the SERS substrate (102) with a fluid (sample) comprising analyte (108) and such competitor molecules (106); radiating (203) the SERS substrate (102) with a light source while measuring a SERS signal; and determining (205) a concentration of the analyte (108) based on the measured signal level.

A corresponding device and system are also provided.

Claims

1. A method of determining the concentration of a predefined analyte in a fluid or fluid sample, the method comprising:

a) providing a SERS substrate comprising a plurality of metal nanostructures and predefined receptor molecules capable of binding predefined competitor molecules, the receptor molecules being bound to the metal nanostructures, each of the competitor molecules being a molecule capable of reversibly binding to either of an analyte molecule and a receptor molecule, but being incapable of simultaneously binding both an analyte molecule and a receptor molecule;

b) contacting the SERS substrate with the fluid or fluid sample comprising said analyte in a concentration to be determined and comprising a predetermined amount of said competitor molecules, such that the amount of competitor molecule bound to the receptor molecules at the metal nanostructures is an inverse function of the amount of analyte in the fluid or fluid sample, and such that when a competitor molecule is not bound to a receptor molecule, it is free to diffuse away from the metal nanostructures;

c) radiating the SERS substrate with a monochromatic light source thereby generating a SERS signal having a level indicative of the amount of competitor molecules bound to the receptor molecules of the SERS substrate;

d) determining the level of the SERS signal while radiating the SERS substrate with the monochromatic light source;

e) determining a concentration of the analyte in the fluid or fluid sample based on the level of the measured SERS signal.

2. The method according to claim 1, wherein the receptor molecules are surface bound reversibly-binding diol-receptors for the competitor molecules.

3. The method according to claim 1, wherein the competitor molecules are boronic acid derivatives.

4. The method according to claim 3, wherein the competitor molecules are boronic acid derivatives comprising a phenyl ring.

5. The method according to claim 1, wherein measuring the level of the SERS signal comprises measuring the level of the SERS signal originating from the competitor molecules bound to the receptor molecules, using a Raman spectrometer.

6. The method according to claim 1, wherein radiating the SERS substrate with a monochromatic light source comprises illuminating the SERS substrate through the dermis of skin tissue so as to generate surface enhanced Raman scattering light originating from the SERS substrate.

7. The method according to claim 1, wherein the SERS substrate is a SiO₂ substrate comprising metal nanostructures on the substrate surface.

8. The method according to claim 1, wherein the SERS substrate is pre-implanted, and wherein the steps b) to e) are performed in vivo.

9. The method according to claim 1, wherein the analyte is glucose.

10. The method according to claim 1, wherein determining a concentration of the analyte in the fluid or fluid sample includes correlating the level of the measured SERS signal with the amount of competitor molecules.

11. The method according to claim 1, wherein a container is disposed atop the SERS substrate, the container comprising the competitor molecules, and wherein the SERS substrate is encapsulated in a biocompatible package comprising a membrane configured to allow the analyte molecules to pass through and to prohibit the competitor molecules to pass through.

12. The method according to claim 1, wherein the SERS substrate comprises metal nanostructures on the substrate surface.

13. The method according to claim 1, wherein

the analyte is glucose;

the competitor molecules are boronic acid derivatives;

the receptor molecules are surface immobilized reversibly-binding diol-receptors capable of binding the competitor molecules.

14. The method according to claim 13, wherein the competitor molecules are boronic acid derivatives comprising a phenyl ring.

15. The method according to claim 14, wherein the SERS substrate comprises metal nanostructures on the substrate surface.

16. The method according to claim 14, wherein the diol-receptors are glucose moieites immobilized on the SERS substrate.

17. The method according to claim 14, wherein the diol-receptors are molecules 2 nm or smaller in size.

18. The method according to claim 14, wherein the diol-receptors are covalently bound to the metal nanostructures.