# US 9,435,803 B2 · Optical resonator diagnostic device and methods of use

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- Number: US 9,435,803 B2
- Document ID: US9435803B2
- Status: Granted
- Kind: B2
- Application number: 13/684,020
- Filed: 2012-11-21
- Published: 2013-05-23
- Granted: 2016-09-06
- Earliest claimed: 2011-11-21
- Assignees: California Institute of Technology
- Applicants: California Institute of Technology
- Inventors: Axel Scherer; Samuel Njoroge; Jingqing Huang
- Web page: https://patentgrep.com/patent/US9435803B2

## CPC

- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- A61B 5/1459: invasive, e.g. introduced into the body by a catheter
- G01N 21/41: Refractivity; Phase-affecting properties, e.g. optical path length (G01N21/21 takes precedence)
- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- G01N 33/552: Glass or silica
- A61B 5/1491: Heated applicators
- A61B 2562/0233: Special features of optical sensors or probes classified in A61B5/00
- A61B 2562/043: in a linear array
- G01N 2201/068: Optics, miscellaneous
- G01N 2201/08: Optical fibres; light guides
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

An implantable diagnostic device in accordance with the present disclosure provides various benefits such as a compact size thereby allowing implanting of the device inside animate objects; low cost due to incorporation of inexpensive detection circuitry and the use of conventional IC fabrication techniques; re-usability by heating thereby allowing multiple diagnostic tests to be performed without discarding the device; and a configuration that allows performing of simultaneous and/or sequential diagnostic tests for detecting one or more similar or dissimilar target molecules concurrently or at different times.

## Claims

### Claim 1

A diagnostic device fabricated in silicon, the diagnostic device comprising:
a first optical nanobeam resonator, made of silicon, the first optical nanobeam resonator comprising a first capture agent located at a first binding site;
an optical waveguide, made of silicon, the optical waveguide configured for propagating a laser beam and for coupling a first portion of the propagated laser beam into the first optical nanobeam resonator; and
a first detector configured for detecting a) a first resonant wavelength generated by the first optical nanobeam resonator when no binding reaction is present at the first binding site, and b) a second resonant wavelength generated by the first optical nanobeam resonator upon undergoing a change in refractive index when a binding reaction is present at the first binding site,
wherein the first optical nanobeam resonator is comprised of one or more substantially circular holes on a surface of the optical waveguide.

### Claim 2 (depends on 1)

The diagnostic device of claim 1, wherein detecting the first resonant wavelength comprises detecting a first current in the detector, and detecting the second resonant wavelength comprises detecting a change in the first current.

### Claim 3 (depends on 1)

The diagnostic device of claim 1, wherein the diagnostic device is packaged for placement inside an animate object, the placement comprising placing the diagnostic device in a blood stream or in tissue close to the bloodstream of the animate object for label-free diagnostic testing.

### Claim 4 (depends on 3)

The diagnostic device of claim 3, wherein the first capture agent is an aptamer selected to capture a first analyte and wherein the second resonant wavelength is shifted from the first resonant wavelength in direct proportion to a concentration of the first analyte.

### Claim 5 (depends on 1)

The diagnostic device of claim 1, further comprising:
a heating element configured for heating at least a portion of the first optical nanobeam resonator.

### Claim 6 (depends on 5)

The diagnostic device of claim 5, wherein the optical waveguide is configured at least in part, to be operative as the heating element.

### Claim 7 (depends on 5)

The diagnostic device of claim 5, further comprising:
a calorimeter for measuring a temperature of the first binding site.

### Claim 8 (depends on 7)

The diagnostic device of claim 7, wherein the calorimeter is an integral part of the first optical nanobeam resonator.

### Claim 9 (depends on 8)

The diagnostic device of claim 8, wherein the calorimeter employs a thermo-optic measurement.

### Claim 10 (depends on 9)

The diagnostic device of claim 9, wherein the thermo-optic measurement provides at least one of: a) a temperature indication of a surface or b) a chemistry of the surface.

### Claim 11 (depends on 10)

The diagnostic device of claim 10, wherein the thermo-optic measurement is a micro-calorimetric measurement confinable to an area of less than 1 micrometer in all directions.

### Claim 12 (depends on 1)

The diagnostic device of claim 1, further comprising:
a second optical resonator comprising a second binding site, the second optical resonator configured to receive a second portion of the laser beam propagated through the optical waveguide; and
a second detector configured for detecting a) a third resonant wavelength generated by the second optical resonator when no binding reaction is present at the second binding site, and b) a fourth resonant wavelength generated by the second optical resonator upon undergoing a change in refractive index when a binding reaction is present at the second binding site.

### Claim 13 (depends on 12)

The diagnostic device of claim 12, wherein the third resonant wavelength is the same as the first resonant wavelength, and the fourth resonant wavelength is the same as the second resonant wavelength.

### Claim 14 (depends on 1)

The diagnostic device of claim 1, further comprising at least one second optical resonator, made of silicon, comprising a second capture agent located at a second binding site, and wherein the first and at least one second optical resonators are located at different holes in the optical waveguide, the holes being located along a longitudinal axis of the optical waveguide, wherein the optical waveguide is made of silicon and the holes are substantially circular.

### Claim 15 (depends on 12)

The diagnostic device of claim 12, wherein the third and fourth resonant wavelengths are different from the first and second resonant wavelengths.

### Claim 16 (depends on 6)

The diagnostic device of claim 6, wherein the heating element is made of metal and is located on a surface of the optical waveguide and on the first optical nanobeam resonator.

### Claim 17 (depends on 1)

The diagnostic device of claim 1, wherein the optical waveguide is a linear optical waveguide.

### Claim 18 (depends on 1)

The diagnostic device of claim 1, wherein the first optical nanobeam resonator is a linear optical nanobeam resonator.
