SERS Nanotag Assays for Multiplexed Biomarker Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic assays face limitations in sensitivity, dynamic range, and complexity, particularly in homogeneous assays which lack sensitivity and are prone to interference, and heterogeneous assays which are labor-intensive and require multiple instruments.
Innovation Solution
The use of Surface Enhanced Raman Scattering (SERS) nanotags in combination with magnetic capture particles to create multiplexed assay platforms that allow for no-wash, fast, and sensitive detection of multiple analytes within biological matrices, enabling simultaneous detection of proteins, DNA, RNA, or small molecules without the need for extensive sample preparation or separation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If homogeneous assay format is used, then assay speed and simplicity are improved, but sensitivity and dynamic range deteriorate
Solution Approach 1:
The patent changes the detection parameter from conventional fluorescence or colorimetric methods to Surface Enhanced Raman Scattering (SERS), which provides significantly higher signal intensity and sensitivity. The SERS effect amplifies the Raman signal by factors of 10^6 to 10^8, enabling detection at much lower analyte concentrations while maintaining the simplicity of homogeneous assay format.
Solution Approach 2:
The patent uses composite nanoparticle structures consisting of metal cores (gold or silver) coated with silica shells, further functionalized with fluorophores and targeting ligands. This composite structure combines the SERS enhancement from metal surfaces with the specificity of antibody-antigen binding, achieving high sensitivity without requiring separation steps.
2Measurement precision
If heterogeneous assay format is used, then sensitivity and dynamic range are improved, but labor intensity and time consumption worsen
Solution Approach 1:
The patent extracts the separation function from the assay protocol by using SERS nanotags that provide such high signal intensity that bound and unbound complexes can be distinguished without physical separation. The high sensitivity of SERS detection allows the assay to proceed in a homogeneous format, eliminating the need to extract or separate bound analyte complexes.
Solution Approach 2:
The patent replaces the mechanical separation steps (washing, magnetic separation, centrifugation) with an optical detection method (SERS). Instead of physically separating bound from unbound complexes, the system uses the enhanced Raman signal to detect the presence of bound complexes directly in the mixture, substituting mechanical operations with optical detection.
3Ease of operation
If conventional detection methods are used, then assay simplicity is maintained, but sensitivity and signal-to-noise ratio worsen
Solution Approach 1:
The patent changes the detection parameter from conventional fluorescence or colorimetric readouts to Raman scattering with surface enhancement. This parameter change provides intrinsic anti-stokes lines that are not present in fluorescence, eliminating background interference and dramatically improving the signal-to-noise ratio while maintaining assay simplicity.
Solution Approach 2:
The patent converts the typically problematic background fluorescence from biological samples into a benefit by using Raman scattering, which does not suffer from fluorescence background. The SERS effect enhances the already weak Raman signal enough to overcome the simplicity trade-off, turning the limitation of Raman's low inherent signal into an advantage by using surface enhancement to achieve both simplicity and high signal-to-noise ratio.
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 enhances sensitivity and reduces assay time and complexity, allowing for the detection of multiple biomarkers in a single assay, improving diagnostic accuracy and efficiency, especially in clinical proteomics and point-of-care settings.
Implementation Method 1
Surface Enhanced Raman Scattering nanotags (SERS nanotags)
Implementation Method 2
concentrating the capture particle/SERS nanotag detection particle complex
Data Source
Figure 1~2
Figure 3
Figure 4
AI summary
Methods and systems for the use of Surface Enhanced Raman Scattering nanotags (SERS nanotags) to create homogeneous (no-wash), heterogeneous or sequence detection assay platforms. In certain embodiments the SERS nanotags are used in combination with magnetic particles. Multiplexed assay platforms are also disclosed. In certain embodiments, the assay is useful for clinical proteomics. Assay platforms suitable for use within a biological matrix, for example within whole blood or serum are also disclosed. The assay formats described herein may be used to detect any analyte of interest including but not limited to the detection of cells, viruses, bacteria, proteins, DNA, RNA, or small molecules in any type of biological (animal or plant kingdom) or environmental samples including but not limited to whole blood or serum, occult samples, urine, feces, air, drinking water, phage, any organism, multicellular clumps of cells, for example, cancer tissue homogenate.