Time-Resolved Spectroscopy for Raman Signal Isolation

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Solution Overview

Problem

Current time-resolved spectroscopy methods face challenges in accurately identifying and quantifying molecules in biological samples due to interference from fluorescence, which overwhelms the Raman signal, making it difficult to measure molecular vibrations effectively.

Innovation Solution

A system and method for time-resolved spectroscopy that uses a tunable excitation light source to illuminate biological samples, detecting Raman scattering and fluorescence at multiple wavelengths, and employing expectation maximization techniques to recover the Raman spectrum by separating it from fluorescence interference, allowing for the identification of molecules using a database of known spectra.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence detection is performed in conventional spectroscopy, then the fluorescence signal is detected, but the Raman signal is overwhelmed and cannot be effectively measured

Engineering Contradiction:
ImproveRaman signal detection accuracyVSAvoidFluorescence interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent segments the detection process into multiple time windows: an early time window to capture instantaneous Raman scattering signals, and a later time window to capture fluorescence signals. This temporal segmentation allows separate measurement of Raman and fluorescence signals that normally overlap, resolving the contradiction by measuring Raman signals before fluorescence interference becomes dominant.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs periodic pulsed excitation light sources with specific duty cycles, turning the light source on and off in periodic intervals. During the 'on' period, Raman signals are captured; during the 'off' period, fluorescence decay is measured. This periodic action separates the measurement of Raman and fluorescence signals in time, enabling accurate Raman detection despite the presence of fluorescence interference.

Inventive Principle:
Principle #19Periodic action

2Measurement precision

If time-resolved spectroscopy with delayed detection is used, then fluorescence interference is reduced, but measurement time increases

Engineering Contradiction:
ImproveRaman signal to fluorescence ratioVSAvoidTotal measurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent maintains continuous measurement by operating in alternating cycles: one cycle measures Raman signals during the excitation pulse, the next cycle measures fluorescence decay after excitation cessation. This continuous alternating measurement approach ensures that both Raman and fluorescence signals are captured over time without idle periods, reducing total measurement time while maintaining signal separation quality.

Inventive Principle:
Principle #20Continuity of useful action

Data Source

PatentUS10876892B2Measuring biological analytes using time-resolved spectroscopy
Publication Date: 2020.12.29 BIOSPEX INC
  • US10876892B2 patent drawing
  • US10876892B2 patent drawing
  • US10876892B2 patent drawing

AI summary

Systems and methods for time-resolved spectroscopy. Exemplary methods include: providing first, second, and third light using an excitation source; receiving first scattered light from a material responsive to the providing the first light; signaling the detector, after a delay, to provide a first spectrum of the received first scattered light; receiving second scattered light from the material responsive to the providing the second light; signaling the detector, after the delay, to provide a second spectrum of the received second scattered light; receiving third scattered light from the material responsive to the providing the third light; signaling the detector, after the delay, to provide a third spectrum of the received third scattered light; recovering a spectrum of the material using the first spectrum, second spectrum, and third spectrum; and identifying at least one molecule of the material using the recovered spectrum and a database of identified spectra.