# US 12,007,328 B2 · Determining extracellular analyte concentration with nanoplasmonic sensors

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- Number: US 12,007,328 B2
- Document ID: US12007328B2
- Status: Granted
- Kind: B2
- Application number: 16/747,702
- Filed: 2020-01-21
- Published: 2020-05-21
- Granted: 2024-06-11
- Earliest claimed: 2015-06-19
- Assignees: The Government of the United States of America, as represented by the Secretary of the Navy
- Applicants: The Government of the United States of America, as represented by the Secretary of the Navy
- Inventors: Marc P. Raphael; Joseph A. Christodoulides; Jeff M. Byers; James B. Delehanty
- Web page: https://patentgrep.com/patent/US12007328B2

## CPC

- G01N 21/648: {using evanescent coupling or surface plasmon coupling for the excitation of fluorescence}
- G01N 21/554: {detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance}
- G01N 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)}
- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- G01N 21/274: {Calibration, base line adjustment, drift correction}
- 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)

## Abstract

Methods and systems for determining extracellular concentration data of an analyte are disclosed. A method for determining extracellular concentration data of an analyte includes receiving sensor data from one or more arrays of functionalized plasmonic nanostructures on a localized surface plasmon resonance imaging chip in contact with a fluid containing at least one living cell for a plurality of times, determining intensity data for the one or more arrays, determining fractional occupancy based on the intensity data, and determining extracellular concentration data based on the fractional occupancy data. A system for determining extracellular concentration data of an analyte includes a LSPRi chip, a sensor component, an intensity component, a fractional occupancy component, a concentration component, and a processor to implement the components.

## Claims

### Claim 1

A computer-implemented system for determining extracellular concentration data of an analyte, the system comprising:
a localized surface plasmon resonance imaging (LSPRi) chip comprising:
a substrate; and
at least one array of functionalized plasmonic nanostructures formed on the substrate, the array of functionalized plasmonic nanostructures being in contact with a fluid containing at least one living cell;
a sensor component for receiving sensor data comprising secretions from the at least one living cell in contact with the one or more arrays of nanostructures for a plurality of times and simultaneously receiving brightfield or fluorescent images of at least one living cell, wherein the sensor component does not include a spectrometer;
an intensity component which determines intensity data for the at least one array of nanostructures, based on the sensor data for each of the plurality of times;
a fractional occupancy component which determines fractional occupancy data for the at least one array of nanostructures based on the intensity data for each of the plurality of times;
a concentration component which determines extracellular concentration data of the analyte based on the fractional occupancy data; and
a processor which implements the components.

### Claim 2 (depends on 1)

The system of claim 1, wherein the system further comprises a movement component which determines the movement of the analyte in the fluid from the extracellular concentration data by mapping the extracellular concentration data for each of the at least one array of nanostructures over the plurality of times.

### Claim 3 (depends on 1)

The system of claim 1, wherein the system further comprises a charge-coupled device positioned to receive emissions from the at least one array of nanostructures.

### Claim 4

A method of determining extracellular concentrations of an analyte in a fluid, the method comprising:
providing at least one array of functionalized plasmonic nanostructures on a localized surface plasmon resonance imaging (LSPRi) chip in contact with a fluid containing at least one living cell;
for each of a plurality of times, receiving sensor data comprising secretions from the at least one living cell in contact with one or more of the arrays of functionalized plasmonic nanostructures and simultaneously receiving brightfield or fluorescent images of at least one living cell, wherein the sensor data is received without the use of a spectrometer;
determining fractional occupancy data for the nanostructures based on the sensor data for each of the plurality of times; and
spatially and temporally mapping extracellular concentration of the analyte based on the fractional occupancy data.