Flexible Plasmonic Grating for Ultra-Sensitive Biomarker Detection

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Solution Overview

Problem

Current medical diagnostic techniques for diseases such as tuberculosis, Zika, Ebola, HIV, and cancer are slow, expensive, and lack sensitivity, particularly in detecting ultra-low concentrations of biomarkers, necessitating the development of a rapid, low-cost, and highly specific diagnostic tool.

Innovation Solution

A flexible plasmonic grating platform that enhances fluorescent intensity by a factor of 100 compared to glass substrates, enabling ultra-sensitive detection of biomarkers down to single-molecule levels through a fluorescent sandwich ELISA assay, using a simple epi-fluorescence microscope and directional excitation/emission coupling, with potential for non-invasive detection in saliva or urine.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional diagnostic methods (culture tests, molecular tests) are used, then detection accuracy is maintained, but detection time is extended to 21 days and equipment cost reaches $17,000

Engineering Contradiction:
Improvedetection timeVSAvoiddetection accuracy
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from conventional methods to surface plasmon resonance (SPR) optical detection, enabling real-time monitoring of biomarker binding events. This optical parameter change allows detection within hours rather than days, while maintaining high sensitivity through resonance angle measurement

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces mechanical/cultural methods (cell culture requiring 21 days) with optical field-based detection (SPR resonance). The mechanical process of bacterial culture is substituted by electromagnetic field interaction with biomolecules, achieving rapid detection without sacrificing accuracy

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If sophisticated molecular diagnostic tests are used, then detection sensitivity is improved, but equipment cost increases to $17,000 and per-test cost reaches $17

Engineering Contradiction:
Improvedetection sensitivityVSAvoidequipment cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent employs disposable SPR sensor chips with pre-immobilized capture antibodies that can be replaced after each use. This eliminates the need for expensive reusable instrumentation while maintaining detection sensitivity, reducing equipment cost from $17,000 to a fraction of that amount

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent introduces an intermediary SPR optical layer that transduces biomolecular binding events into measurable optical signals. This intermediary mechanism enables sensitive detection without requiring expensive PCR instrumentation, bridging the gap between simple detection and sophisticated molecular testing

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If PCR-based detection is used, then biomarker amplification is achieved, but unwanted DNA is also amplified and detection specificity is reduced

Engineering Contradiction:
Improvesignal amplificationVSAvoiddetection specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and isolates the specific biomarker binding event from the complex PCR amplification process. By using SPR to detect only the specific antigen-antibody interaction on the sensor surface, unwanted DNA amplification is excluded, maintaining both signal amplification and detection specificity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the limitation of non-amplifying SPR detection into a benefit by using the label-free nature of SPR to achieve specific detection without amplification artifacts. The lack of DNA amplification becomes an advantage by eliminating false positives from unwanted DNA, while sufficient signal is obtained through direct binding detection

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

The solution provides early, inexpensive, and highly specific diagnosis of diseases like tuberculosis with results in under three hours, significantly reducing equipment costs and detection time, while maintaining high sensitivity and adaptability to various diseases.

Implementation Method 1

The plasmonic grating is capable of enhancing the fluorescent intensity by a factor of at least 100 as compared to a glass substrate. This enhancement is the result of excellent light coupling properties and superior signal-to-noise ratio of the novel plasmonic grating.

Methodology Applied
Scientific EffectSurface plasmon resonance:

Implementation Method 2

Some embodiments of the system are based on a fluorescent sandwich ELISA assay (or other assay technique such as a competitive binding fluoroimmunoassay) performed on the plasmonic grating platform incorporated with a fluorescence detection unit

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11796473B2Detection of biomarkers using plasmonic gratings
Publication Date: 2023.10.24 THE CURATORS OF THE UNIVERSITY OF MISSOURI
  • US11796473B2 patent drawing
  • US11796473B2 patent drawing
  • US11796473B2 patent drawing

AI summary

The invention broadly relates techniques for imaging and medical diagnosis and, more particularly, to the fabrication of flexible plasmonic gratings and the use thereof in detection of biomarkers. A first aspect of the invention provides for techniques for the fabrication of novel, flexible plasmonic gratings that can be inexpensively fabricated onto fiber optic cables, flexible films and substrates with non-uniform surfaces to enhance the imaging resolution. A second aspect of the invention provides for an ultra¬high sensitivity (single molecule counting) biomarker detection platform useable for medical diagnosis based on a fluorescent sandwich ELISA assay performed on a plasmonic grating platform incorporated with a fluorescence detection unit.