Optical real-time biosensor

Inventors: Amani Hariri (Stanford, CA); Constantin Dory (Stanford, CA); Alyssa Cartwright (Stanford, CA); Jelena Vuckovic (Palo Alto, CA); Hyongsok Tom Soh (Palo Alto, CA)

Assignees: CZ Biohub SF, LLC; The Board of Trustees of the Leland Stanford Junior University

G01N21/6486 A61B5/0059 A61B5/1455 A61B5/6801 A61B5/6846 G01N21/648 G01N2021/6441 G01N2021/6484

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Quick Facts

Patent No.: US 12710369
App. No.: 18/589,897
Granted: Aug 18, 2026
Kind: B2

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Abstract

The disclosure provides an optical probe comprising an optical waveguide attached to a molecular switch that produces an altered optical signal upon binding a target molecule. The disclosure also provides an optical sensor system comprising an optical probe, a light source configured to emit the excitation light to be coupled into the optical waveguide of the optical probe; and a detector.

Claims (34)

1 . An optical sensor system wearable or implantable in a living subject, comprising:

an optical probe, comprising:

an optical waveguide having a first end and a second end, the first end configured to receive an excitation light to be propagated through the optical waveguide and to be emitted from the second end or a middle region into a surrounding medium;

one or more molecular switches attached to a facet or a sidewall of the second end or the middle region of the optical waveguide, wherein the one or more molecular switches are configured to change conformation upon binding to a corresponding target molecule; and

one or more optical reporters, each of the one or more optical reporters attached to a respective molecular switch and configured, when exposed to the excitation light, to produce an optical signal that changes upon binding of the respective molecular switch to the corresponding target molecule in the surrounding medium, wherein the optical signal is coupled back into the optical waveguide and propagated through the optical waveguide to be emitted from the first end or second end;

a light source configured to emit the excitation light to be coupled into the optical waveguide of the optical probe; and

a detector configured to (i) receive the one or more optical signals produced by the one or more optical reporters that are transmitted through the optical waveguide, and (ii) detect changes of the one or more optical signals, thereby allowing for detection of a concentration of the corresponding target molecule.

2 . The optical sensor system of claim 1 , wherein the optical waveguide comprises an optical fiber.

3 . The optical sensor system of claim 2 , wherein the optical fiber comprises one of a single-mode optical fiber, a step-index multimode optical fiber, or a graded-index multimode optical fiber.

4 . The optical sensor system of claim 1 , wherein at least a first molecular switch of the one or more molecular switches is attached to the sidewall of the second end of the optical waveguide, and the optical reporter attached to the first molecular switch is exposed to an evanescent optical field of the excitation light adjacent the sidewall.

5 . The optical sensor system of claim 4 , wherein the optical signal is propagated through the optical waveguide to be emitted from the first end.

6 . The optical sensor system of claim 4 , wherein the evanescent optical field extends to a distance less than one micron from the sidewall.

7 . The optical sensor system of claim 1 , wherein at least a first molecular switch of the one or more molecular switches is attached to the sidewall of the middle region of the optical waveguide, and the optical reporter attached to the first molecular switch is exposed to an evanescent optical field of the excitation light adjacent the sidewall.

8 . The optical sensor system of claim 7 , wherein the optical signal is propagated through the optical waveguide and is emitted from the second end.

9 . The optical sensor system of claim 1 , wherein the one or more optical reporters comprise one or more fluorescent labels.

10 . The optical sensor system of claim 9 , wherein the one or more fluorescent labels comprise a donor fluorophore and an acceptor fluorophore that interact with each other to emit fluorescence light when the respective molecular switch attached thereto changes conformation.

11 . The optical sensor system of claim 1 , wherein each molecular switch comprises a nucleic acid, a protein, a polymer comprising nucleic acids and proteins, or a chemically modified version thereof.

12 . The optical sensor system of claim 1 , wherein:

the one or more molecular switches comprise at least a first molecular switch and a second molecular switch, wherein the first molecular switch changes conformation upon binding to a first target molecule, and the second molecular switch changes conformation upon binding to a second target molecule; and

the one or more optical reporters comprise at least a first optical reporter and a second optical reporter, wherein the first optical reporter is attached to the first molecular switch and configured to produce a first optical signal in a first wavelength range upon binding to the first target molecule, and the second optical reporter is attached to the second molecular switch and configured to produce a second optical signal in a second wavelength range different from the first wavelength range upon binding to the second target molecule.

13 . The optical sensor system of claim 1 , wherein the excitation light is in a first wavelength range, and the one or more optical signals produced by the one or more optical reporters are in a second wavelength range different from the first wavelength range, and the optical sensor system further comprising an optical filter coupled to the detector and configured to transmit the one or more optical signals in the second wavelength range and block the excitation light in the first wavelength range.

14 . The optical sensor system of claim 1 , wherein the excitation light is in a first wavelength range, wherein the one or more optical signals produced by the one or more optical reporters are in a second wavelength range different from the first wavelength range, and the detector comprises an optical spectrometer.

15 . The optical sensor system of claim 1 , wherein the detector comprises a single photon counting module (SPCM).

16 . The optical sensor system of claim 15 , wherein a power of the excitation light emitted by the light source ranges from about 1 nW to about 300 nW, or from about 10 nW to about 200 nW, or from about 40 nW to about 150 nW, or from about 50 nW to about 100 nW.

17 . The optical sensor system of claim 1 , wherein the optical probe further comprises a tube surrounding the second end of the optical waveguide, the tube being configured to protect the second end of the optical waveguide when inserted into the living subject.

18 . The optical sensor system of claim 1 , wherein the optical sensor system comprises at least a first optical probe and a second optical probe, wherein the optical probe is either the first optical probe or the second optical probe, wherein

the first optical probe comprises:

a first optical waveguide having a first end and a second end, the first end configured to receive excitation light to be propagated through the first optical waveguide and to be emitted from the first end or the second end into a surrounding medium;

one or more first molecular switches attached to a facet or a sidewall of the second end or a middle region of the optical waveguide, wherein the one or more first molecular switches are configured to change conformation upon binding to a corresponding first target molecule; and

one or more first optical reporters, each of the one or more first optical reporters attached to a respective molecular switch and configured, when exposed to the excitation light, to produce a first optical signal that changes upon binding of the respective molecular switch to the corresponding first target molecule in the surrounding medium, wherein the first optical signal is coupled back into the optical waveguide via the second end and propagated through the optical waveguide to be emitted from the first end or the second end; and

the second optical probe comprises:

a second optical waveguide having a first end and a second end, the first end configured to receive excitation light to be propagated through the second optical waveguide and to be emitted from the first end or the second end into a surrounding medium;

one or more second molecular switches attached to a facet or a sidewall of the second end or a middle region of the second optical waveguide, wherein the one or more second molecular switches are configured to change conformation upon binding to a corresponding second target molecule; and

one or more second optical reporters, each of the one or more second optical reporters attached to a respective molecular switch and configured, when exposed to the excitation light, to produce a second optical signal that changes upon binding of the respective molecular switch to the corresponding second target molecule in the surrounding medium, wherein the second optical signal is coupled back into the optical waveguide via the second end and propagated through the second optical waveguide to be emitted from the first end or the second end.