Optical Analyte Detection Using Photosensitizer State-Change Signals
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Solution Overview
Problem
Existing immunoassays face limitations in detecting low concentrations of analytes due to factors such as signal saturation, high-dose hook effect, non-specific binding, and complex, costly instrumentation, especially when dealing with samples containing cellular materials.
Innovation Solution
A method involving a substrate with an optical component and a binding component, where a reporter reagent with a photosensitizer binds to the substrate, and upon irradiation with electromagnetic radiation, the optical component changes state, allowing for the detection of local regions indicative of analyte concentration without wash steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional immunoassays are used to detect analytes, then binding events can be measured, but signal saturation and high-dose hook effect occur at high analyte concentrations
Solution Approach 1:
The invention divides the detection process into discrete digital units by confining reactions to individual microwells, where each well contains at most one bead-antigen-reporter complex. This segmentation prevents signal saturation because each well contributes a binary signal (positive/negative) rather than a cumulative analog signal that saturates at high analyte concentrations.
Solution Approach 2:
The invention transitions from traditional planar or bulk solution assays to a three-dimensional hierarchical structure: microparticles (beads) suspended in solution within arrays of picoliter-scale microwells. This dimensional transformation enables digital counting of binding events while maintaining solution-phase kinetics, resolving the contradiction between sensitivity and high-concentration reliability.
2Measurement precision
If wash steps are performed to remove excess reporter, then non-specific binding is reduced, but assay complexity and time increase
Solution Approach 1:
The invention extracts the separation function from the assay procedure by using physical confinement in microwells. Excess reporter particles remain in the bulk solution phase while bound complexes are trapped in microwells, enabling automatic separation without wash steps. This eliminates the need for manual or automated washing while maintaining high signal-to-noise ratios.
Solution Approach 2:
The microwell array structure provides self-separation functionality through its geometric design. The picoliter-scale wells naturally confine bound complexes while excluding excess reagents, making the separation process self-executing without external intervention. This self-service mechanism reduces assay complexity while preserving measurement precision.
3Measurement precision
If sensitive detection of low analyte concentrations is achieved, then detection limit is improved, but instrumentation cost and complexity increase
Solution Approach 1:
The invention uses optical copying/detection of light signals from fluorescent or colorimetric reporters in microwells. Instead of complex mass spectrometry or highly specialized equipment, simple optical detectors capture light emission or absorption changes, providing sensitive detection at low analyte concentrations using cost-effective, widely available instrumentation.
Solution Approach 2:
The invention employs colorimetric or fluorescent reporters that produce visible optical signals upon binding to the analyte. These color/fluorescence changes can be detected by simple optical detectors, enabling sensitive detection of low analyte concentrations without requiring complex instrumentation. The optical signal amplification allows attomolar detection using basic laboratory equipment.
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 method enables sensitive, cost-effective detection of analytes down to attomolar levels in various samples, including those with cellular materials, by simplifying the assay process and reducing the need for complex instrumentation.
Implementation Method 1
irradiating the device with electromagnetic radiation for absorption by the optical component and for absorption by the photosensitiser of the reporter reagent, such that the optical component absorbs electromagnetic radiation to generate an excited optical component
Implementation Method 2
the photosensitiser of the reporter reagent bound to the surface of the substrate absorbs electromagnetic radiation and interacts with the excited optical component to cause the excited optical component to change from a first optical state to a second optical state
Data Source
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AI summary
The present invention provides a method for detecting an analyte in a sample, the method comprising the steps of: (i) providing a mixture comprising a sample and a reporter reagent to a device, wherein the reporter reagent comprises a photosensitiser, the device comprising a substrate having an optical component and a binding component, wherein the optical component and the binding component are attached to a surface of the substrate; (ii) allowing a portion of the reporter reagent to bind to the surface of the substrate in proportion to the concentration of the analyte, by means of the binding component; (iii) irradiating the device with electromagnetic radiation for absorption by the optical component and for absorption by the photosensitiser of the reporter reagent, such that the optical component absorbs electromagnetic radiation to generate an excited optical component, and the photosensitiser of the reporter reagent bound to the surface of the substrate absorbs electromagnetic radiation and interacts with the excited optical component to cause the excited optical component to change from a first optical state to a second optical state, thereby forming a set of local regions having the second optical state on the substrate; and (iv) detecting the set of local regions having the second optical state on the substrate.