Fluorescent Nanodiamond Assay Modulation for Background Fluorescence
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Solution Overview
Problem
Fluorescence-based lateral flow assays are limited by background fluorescence from substrates and matrices, necessitating the development of ultra-sensitive methods for detecting biomarkers in disease diagnosis and monitoring.
Innovation Solution
The use of fluorescent nanodiamonds (FNDs) with externally modulated fluorescence, combined with a lock-in amplification algorithm or Fourier transform analysis, to enhance the signal-to-background ratio and improve detection sensitivity in in vitro diagnostic assays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional fluorescence-based lateral flow assays are used, then the assay can be performed with simple equipment and procedures, but the background fluorescence from substrate and matrix limits the detection sensitivity
Solution Approach 1:
The patent applies periodic modulation of the fluorescent label's emission properties at a specific frequency, allowing the signal to be varied in time while the background fluorescence remains constant. This periodic action enables frequency-based separation of signal from background, dramatically improving detection sensitivity by up to 810-fold in signal-to-noise ratio.
Solution Approach 2:
The patent changes the temporal parameter of the fluorescent signal by modulating its emission at a characteristic frequency. This parameter change transforms the static fluorescence measurement into a dynamic, frequency-encoded signal that can be distinguished from the static background fluorescence through frequency domain analysis, achieving ultra-sensitive detection down to 10^-19 M.
2Measurement precision
If fluorescence modulation and frequency domain analysis are implemented, then the signal-to-noise ratio is enhanced by up to 810-fold, but the device complexity and procedural steps increase
Solution Approach 1:
The patent replaces complex mechanical or chemical separation methods with electromagnetic field-based frequency modulation and detection. By using frequency domain analysis and lock-in amplification algorithms, the system achieves high signal-to-noise ratio enhancement without requiring physically complex separation apparatus, thus managing device complexity while improving measurement precision.
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
This approach achieves a significant improvement in sensitivity, with up to 810-fold enhancement in signal-to-noise ratio and 380-fold improvement in limit of detection, enabling the detection of biomolecular concentrations down to 10^-19 M, surpassing the sensitivity of traditional fluorescence-based assays.
Implementation Method 1
a fluorescent label whose fluorescence can be externally modulated
Implementation Method 2
applying a frequency domain analysis, such as a lock-in amplification algorithm or Fourier transform, to the fluorescence time series
Data Source
AI summary
An in vitro diagnostic assay method, comprising: providing a sample which may comprise target analyte(s); contacting the sample with a fluorescent label whose fluorescence can be externally modulated, such that the fluorescent label is associated with target analyte(s), if present, to form a fluorescent label-analyte complex; and detecting the fluorescent label-analyte complex; and device, kit and solid phase for performing an in vitro diagnostic assay method.