# US 2024/0201084 A1 · Pixel-Diversity Nanoparticle Detection by Interferometric Reflectance Imaging Sensor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0201084 A1 - Document ID: US20240201084A1 - Status: Published application - Kind: A1 - Application number: 18/544,361 - Filed: 2023-12-18 - Published: 2024-06-20 - Earliest claimed: 2022-12-19 - Assignees: Trustees of Boston University - Applicants: Trustees of Boston University - Inventors: M. Selim Ünlü; Iris Celebi; Mete Aslan - Web page: https://patentgrep.com/patent/US20240201084A1 ## CPC - G01N 21/45: using interferometric methods; using Schlieren methods - G01B 9/02011: {using temporal polarization variation} - G01B 9/02041: {characterised by particular imaging or detection techniques} - G01N 21/21: Polarisation-affecting properties (G01N21/19 takes precedence) - G01N 21/55: Specular reflectivity - G01N 2201/06153: the sources being LED's - 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) - G01B: MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS ## Abstract Aspects of inventive concepts described herein relate to an interferometric reflectance imaging system. The system can include an imaging sensor including pixels that are preferentially sensitive to a plurality of light components; an illumination source configured to emit illumination light along an illumination path, the illumination light including the plurality of light components; and a target including a target substrate configured to support one or more nanoparticles on a surface of the target substrate. The system may be configured to, at a nominal focus position: generate an image at the imaging sensor based, at least in part, on the light reflected from the target interfering with light scattered from nanoparticles on the target substrate; and process the image to detect the nanoparticles on the target substrate. ## Claims ### Claim 1 An interferometric reflectance imaging system for detection of nanoparticles comprising: an imaging sensor comprising pixels that are preferentially sensitive to a plurality of light components; an illumination source configured to emit illumination light along an illumination path, the illumination light comprising the plurality of light components; and a target comprising a target substrate configured to support one or more nanoparticles on a surface of the target substrate, the target configured to receive the illumination light from the illumination path and reflect light along a collection path toward the imaging sensor, each nanoparticle on the target substrate producing reflected light with different characteristics for each one of the plurality of light components of the illumination light, wherein the system is configured to, at a nominal focus position: generate an image at the imaging sensor based, at least in part, on the light reflected from the target interfering with light scattered from nanoparticles on the target substrate; and process the image to detect the nanoparticles on the target substrate. ### Claim 2 (depends on 1) The imaging system of claim 1, wherein the plurality of light components emitted by the illumination source are different spectra of light and the imaging sensor is a multi-spectral camera. ### Claim 3 (depends on 2) The imaging system of claim 2, wherein the illumination source includes two or more narrow-band light sources. ### Claim 4 (depends on 3) The imaging system of claim 3, wherein the narrow-band light sources are LED sources, each LED source emitting light at a different wavelength. ### Claim 5 (depends on 2) The imaging system of claim 2, wherein the different spectra of light are red, blue, and green in the visible spectrum and the imaging sensor is a color camera. ### Claim 6 (depends on 1) The imaging system of claim 1, wherein the nanoparticles are biological nanoparticles. ### Claim 7 (depends on 6) The imaging system of claim 6, wherein the nanoparticles include at least one of viruses, exosomes, or other macromolecules. ### Claim 8 (depends on 1) The imaging system of claim 1, wherein the nanoparticles include at least one of a gold nanosphere, a dielectric nanoparticle, or any other type of artificial nanoparticle. ### Claim 9 (depends on 1) The imaging system of claim 1, wherein the nanoparticles have dimensions in a range of about 10 to about 100 nanometers. ### Claim 10 (depends on 1) The imaging system of claim 1, wherein the plurality of light components of the illumination light emitted by the illumination source are different polarizations of light and the imaging sensor is a polarization camera. ### Claim 11 (depends on 10) The imaging system of claim 10, wherein the polarization camera comprises pixels nominally sensitive to 0, 45, 90, and 135 degrees of linearly polarized light. ### Claim 12 (depends on 10) The imaging system of claim 10, wherein the illumination source emits randomly polarized light. ### Claim 13 (depends on 10) The imaging system of claim 10, wherein the illumination source comprises an LED light source. ### Claim 14 (depends on 10) The imaging system of claim 10, wherein the nanoparticles are rod-shaped nanoparticles. ### Claim 15 (depends on 14) The imaging system of claim 14, wherein the rod-shape nanoparticles are gold nanorods. ### Claim 16 (depends on 15) The imaging system of claim 15, wherein the gold nanorods have dimensions in a range of about 10 to about 100 nanometers. ### Claim 17 (depends on 14) The imaging system of claim 14, wherein the illumination source is a narrow spectrum light source configured to emit light with characteristics matching the optical resonance of the rod-shaped nanoparticles. ### Claim 18 (depends on 17) The imaging system of claim 17, wherein the illumination source comprises an LED light source with an emission spectrum nominally matching the optical resonance of the gold nanorods on the surface of the target substrate. ### Claim 19 (depends on 10) The imaging system of claim 10, wherein the imaging sensor comprises at least one superpixel, each superpixel comprising: a first pixel configured to be selectively sensitive to linearly polarized light along a first axis; a second pixel configured to be selectively sensitive to linearly polarized light oriented 45 degrees relative to the first axis; a third pixel configured to be selectively sensitive to linearly polarized light oriented 90 degrees relative to the first axis; and a fourth pixel configured to be selectively sensitive to linearly polarized light oriented 135 degrees relative to the first axis. ### Claim 20 (depends on 1) The imaging system of claim 1, wherein the imaging sensor is configured to form at least one image and the imaging system further comprises a processor configured to analyze the at least one image from the imaging sensor. ### Claim 21 (depends on 1) The imaging system of claim 1, wherein the target substrate includes a base substrate having a first reflecting surface and a transparent spacer layer having a first surface in contact with the first reflecting surface and a second reflecting surface on a side opposite to the first surface, and wherein the transparent spacer layer has a predefined thickness that is determined as a function of a wavelength of the illuminating light and produces a predefined radiation pattern of optical scattering when nanoparticles are positioned on or near the second reflective surface. ### Claim 22 (depends on 1) The imaging system of claim 1, wherein the imaging sensor comprises pixels that are diverse in sensitivity to the plurality of light components, a first type of the pixels being preferentially sensitive to a first component of the plurality of light components, a second type of the pixels being preferentially sensitive to a second component of the plurality of light components. ### Claim 23 (depends on 1) The imaging system of claim 1, wherein, at a nominal focus position, the system is configured to process the image to extract one or more optical properties of the nanoparticles on the target substrate. ### Claim 24 A method for detection of nanoparticles, comprising: providing a target comprising a target substrate and one or more nanoparticles on the surface of the target substrate; illuminating the target substrate with a multitude of light components along an illumination path; collecting light reflected and scattered from the target on an imaging sensor comprising pixels preferentially sensitive to the plurality of light components; at a nominal focus point: generating an image at the imaging sensor based on interference of the light reflected and scattered from the target; and processing the image to detect the nanoparticles on the target substrate. ### Claim 25 (depends on 24) The method of claim 24, wherein the imaging sensor comprises pixels that are diverse in sensitivity to the plurality of light components, a first type of the pixels being preferentially sensitive to a first component of the plurality of light components, a second type of the pixels being preferentially sensitive to a second component of the plurality of light components. ### Claim 26 (depends on 24) The method of claim 24, wherein the processing the image comprises calculating a variance for each pixel. ### Claim 27 (depends on 24) The method of claim 24, wherein the imaging sensor comprises at least one superpixel, each superpixel comprising: a first pixel configured to be selectively sensitive to linearly polarized light along a first axis; a second pixel configured to be selectively sensitive to linearly polarized light oriented 45 degrees relative to the first axis; a third pixel configured to be selectively sensitive to linearly polarized light oriented 90 degrees relative to the first axis; and a fourth pixel configured to be selectively sensitive to linearly polarized light oriented 135 degrees relative to the first axis. ### Claim 28 (depends on 27) The method of claim 27, wherein the processing the image comprises calculating a signal for each superpixel based on a square of the difference between an intensity collected at the third pixel and an intensity collected at the first pixel added to a square of the difference between an intensity collected at the fourth pixel and an intensity collected at the second pixel. ### Claim 29 (depends on 24) The method of claim 24, further comprising, at a nominal focus point, processing the image to extract one or more optical properties of the nanoparticles on the target substrate. ### Claim 30 An interferometric reflectance imaging system for detection of nanoparticles comprising: an imaging sensor comprising pixels that are diverse in sensitivity to a plurality of light components, a first type of the pixels being preferentially sensitive to a first component of plurality of light components, a second type of the pixels being preferentially sensitive to a second component of the plurality of light components; an illumination source configured to emit illumination light along an illumination path, the illumination light comprising the plurality of light components; a target comprising a target substrate configured to support one or more nanoparticles on a surface of the target substrate, the target configured to receive the illumination light from the illumination path and reflect light along a collection path toward the imaging sensor, each nanoparticle on the target substrate producing reflected light with different characteristics for each one of the plurality of light components of the illumination light; and a processor configured to receive an image from the imaging sensor and process the received image to identify at least one high contrast area that corresponds to at least one of the nanoparticles, wherein the high contrast area includes a pixel value substantially different from values in neighboring pixels.