Parallel LSPR Nanostructure Calibration via Array Imaging

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Solution Overview

Problem

The calibration of hundreds or thousands of individual nanostructures for quantitative analysis in localized surface plasmon resonance (LSPR) imaging is time-consuming and impractical, as each nanostructure must be sequentially calibrated for accurate quantification of biochemical parameters like kinetic rate constants and analyte concentration.

Innovation Solution

A method for calibrating multiple nanostructures in parallel using a chip with patterned plasmonic nanostructures, allowing for simultaneous data collection and analysis through CCD-based LSPR imagery and spectral data, which determines the fractional occupancy of surface-bound receptors with nanomolar sensitivity and temporal resolution of 225 ms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sequential calibration of individual nanostructures is performed, then measurement precision is improved, but productivity deteriorates due to time-consuming calibration process

Engineering Contradiction:
Improvequantification accuracyVSAvoidcalibration speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent merges the calibration of multiple individual nanostructures into a single batch-mode imaging process. Instead of calibrating each nanostructure separately, the system captures images of entire arrays of nanostructures simultaneously and uses statistical analysis to extract calibration parameters for all structures in parallel, thereby maintaining measurement precision while dramatically improving productivity

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses the assumption that individual nanostructures within an array are identical copies with uniform properties. By measuring the ensemble response of the array and statistically analyzing the data, the system infers calibration parameters for individual nanostructures without needing to calibrate each one separately, thus achieving both precision and high throughput

Inventive Principle:
Principle #26Copying

2Productivity

If batch-mode calibration is used, then productivity is improved through simultaneous data collection, but measurement precision deteriorates due to the complexity of analyzing ensemble data

Engineering Contradiction:
Improvecalibration throughputVSAvoidquantification accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent implements a feedback mechanism where the measured optical responses from the nanostructure array are fed into a statistical analysis algorithm. The system iteratively adjusts calibration parameters to minimize the difference between predicted and observed ensemble responses, thereby extracting accurate individual nanostructure calibration data from the collective measurements

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent transforms the calibration problem by changing from direct measurement of individual nanostructures to statistical inference from ensemble data. By analyzing the distribution and variance of optical responses across the array, the system extracts calibration parameters that accurately represent individual nanostructures while maintaining high productivity

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables the mapping of fractional occupancy of surface-bound receptors at individual nanostructures with high sensitivity and temporal resolution, facilitating the quantitative analysis of biochemical parameters without the need for sequential calibration, and is compatible with complex environments like live-cell microscopy.

Implementation Method 1

The utilization of the localized surface plasmon resonance (LSPR) observed in metallic nanostructures for label-free biosensing

Methodology Applied
Scientific EffectLocalized surface plasmon resonance (LSPR): Resonance

Implementation Method 2

The chip is used to collect charge coupled device-based (CCD-based) LSPR imagery data of each individual nanostructure and LSPR spectral data of the array

Methodology Applied
Scientific EffectLSPR spectral measurement: Absorption Spectroscopy

Data Source

PatentEP2901136B1Calibrating single plasmonic nanostructures for quantitative biosensing
Publication Date: 2019.11.06 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • EP2901136B1 patent drawingFigure 1a~1c
  • EP2901136B1 patent drawingFigure 2a~2c
  • EP2901136B1 patent drawingFigure 3a~3b

AI summary

A method for calibrating multiple nanostructures in parallel for quantitative biosensing using a chip for localized surface plasmon resonance (LSPR) biosensing and imaging. The chip is a glass coverslip compatible for use in a standard microscope with at least one array of functionalized plasmonic nanostructures patterned onto it using electron beam nanolithography. The chip is used to collect CCD-based LSPR imagery data of each individual nanostructure and LSPR spectral data of the array. The spectral data is used to determine the fractional occupancy of the array. The imagery data is modeled as a function of fractional occupancy to determine the fractional occupancy of each individual nanostructure.