# US 10,481,157 B2 · Optical resonator diagnostic device and methods of use

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- Number: US 10,481,157 B2
- Document ID: US10481157B2
- Status: Granted
- Kind: B2
- Application number: 16/206,294
- Filed: 2018-11-30
- Published: 2019-06-27
- Granted: 2019-11-19
- 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/US10481157B2

## 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:
an array of optical resonators, wherein at least one optical resonator of the array of optical resonators comprises an immunoassay site;
an optical waveguide configured for coupling coherent light into one or more optical resonators in the array of optical resonators; and
at least one detector optically coupled to the at least one optical resonator and configured to detect: a) a first resonant wavelength generated by the at least one optical resonator, and b) a second resonant wavelength generated by the at least one optical resonator upon undergoing a change in refractive index by binding of at least one molecule to the immunoassay site,
wherein each optical resonator comprises a substantially circular hole on a surface of the optical waveguide.

### Claim 2

A diagnostic device fabricated in silicon, the diagnostic device comprising:
an array of optical nanobeam resonators made of silicon, wherein at least one optical nanobeam resonator of the array of optical resonators comprises a capture agent located at a binding site;
an optical waveguide made of silicon, the optical waveguide configured for coupling coherent light into one or more optical nanobeam resonators in the array of optical nanobeam resonators; and
at least one detector optically coupled to the at least one optical resonator and configured to detect: a) a first resonant wavelength generated by the at least one optical nanobeam resonator when no binding reaction is present at the corresponding binding site, and b) a second resonant wavelength generated by the at least one optical nanobeam resonator upon undergoing a change in refractive index when a binding reaction is present at the corresponding binding site,
wherein each nanobeam optical resonator comprises a substantially circular hole on a surface of the optical waveguide.

### Claim 3 (depends on 1)

The diagnostic device of claim 1, wherein the at least one detector generates a first current in response to the first resonant wavelength and a second current in response to the second resonant wavelength.

### Claim 4 (depends on 3)

The diagnostic device of claim 3, wherein the second current is substantially zero when the corresponding optical resonator undergoes the change in refractive index.

### Claim 5 (depends on 1)

The diagnostic device of claim 1, wherein the diagnostic device is packaged in a silicon-based package that is configured for placement inside an animate object.

### Claim 6 (depends on 5)

The diagnostic device of claim 5, wherein the silicon-based package comprises a) a silicon substrate, and b) at least one silicon membrane in which the array of optical resonators is fabricated at least in part, by using a lithographic process.

### Claim 7 (depends on 6)

The diagnostic device of claim 6, further comprising:
a capture agent coated on to at least a portion of the at least one silicon membrane to enable label-free diagnostic testing.

### Claim 8 (depends on 1)

The diagnostic device of claim 1, further comprising:
a plurality of heating elements configured for heating a respective one of the array of optical resonators.

### Claim 9 (depends on 8)

The diagnostic device of claim 8, wherein the heating is directed at non-destructively regenerating at least one of the immunoassay sites for carrying out additional diagnostic tests.

### Claim 10 (depends on 8)

The diagnostic device of claim 8, wherein the heating is directed at obtaining diagnostic data indicative of molecular concentration in a tested fluid.

### Claim 11 (depends on 10)

The diagnostic device of claim 10, wherein the tested fluid is a blood sample and the molecular concentration of a target protein in the blood sample.

### Claim 12 (depends on 1)

The diagnostic device of claim 1, wherein the optical waveguide is a linear optical waveguide, and the array of optical resonators comprises an array of holes in the linear optical waveguide.

### Claim 13 (depends on 12)

The diagnostic device of claim 12, wherein at least a portion of the linear optical waveguide is configured as a heating element for heating one or more of the array of optical resonators.

### Claim 14 (depends on 1)

The diagnostic device of claim 1, wherein the optical waveguide is linear and each optical resonator is in a linear array.

### Claim 15 (depends on 1)

The diagnostic device of claim 1, wherein each optical resonator is an optical nanobeam resonator made of silicon and the optical waveguide is made of silicon.

### Claim 16 (depends on 2)

The diagnostic device of claim 2, wherein the 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 17 (depends on 2)

The diagnostic device of claim 2, further comprising a heating element configured for heating at least a portion of the at least one optical nanobeam resonator.
