Smart Hydrogel Particles for Biomarker Sequestration

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Solution Overview

Problem

Current methods for detecting biomarkers, especially low-abundance proteins in complex biological mixtures like blood and urine, face challenges due to their low concentration and susceptibility to degradation, making early disease detection difficult and inefficient.

Innovation Solution

Development of capture particles, specifically smart hydrogel particles that can selectively sequester biomarkers based on size and affinity, protecting them from degradation and concentrating them for analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods like two-dimensional gel electrophoresis are used to detect biomarkers, then the detection process can be performed with standard equipment, but the sensitivity and resolution are insufficient to detect low abundance biomarkers

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces smart particles as intermediary carriers that selectively bind to low abundance biomarkers through affinity ligands. These particles act as mediators between the complex biological mixture and the detection system, concentrating target molecules while excluding high abundance proteins, thereby enabling detection of previously undetectable biomarkers with standard equipment

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The smart particles utilize porous structures with controlled pore sizes that allow selective penetration based on molecular size. The porous material enables size-based fractionation where low molecular weight biomarkers can enter the particles while high molecular weight proteins are excluded, enhancing detection sensitivity without requiring complex fractionation equipment

Inventive Principle:
Principle #31Porous materials

2Measurement precision

If mass spectrometry is used with high sensitivity, then low abundance proteins can be detected, but the working range is limited and less abundant proteins are masked by more abundant proteins

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection range
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent extracts low abundance biomarkers from the complex biological mixture by selective binding to smart particles. This extraction process separates target molecules from the overwhelming background of high abundance proteins, allowing mass spectrometry to detect low abundance proteins across a broader concentration range without masking effects

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The smart particles change their binding parameters dynamically - they exhibit high affinity for low abundance biomarkers at physiological conditions, then undergo parameter changes during elution to release captured molecules. This enables the system to adapt to different detection requirements and expand the effective working range of mass spectrometry

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high abundance proteins are depleted using immunoaffinity depletion columns, then the concentration range for detection is improved, but the yield of candidate biomarkers is significantly reduced

Engineering Contradiction:
Improveconcentration rangeVSAvoidbiomarker yield
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The smart particles exhibit local quality through their dual functionality: the outer surface provides size-based exclusion properties while the interior contains affinity ligands for specific biomarker binding. This localized functional differentiation allows selective concentration of low abundance biomarkers without requiring depletion of high abundance proteins, preserving biomarker yield while expanding detection range

Inventive Principle:
Principle #3Local quality

4Reliability

If protein biomarkers are subjected to degradation by endogenous or exogenous proteinases, then the biomarkers remain in their original mixture, but the biomarkers are degraded immediately following collection

Engineering Contradiction:
Improvebiomarker integrityVSAvoidprotection mechanism complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The smart particles provide beforehand cushioning by creating a protective microenvironment that shields biomarkers from proteinase degradation. The particle matrix acts as a physical barrier and the controlled release mechanism ensures biomarkers are protected during storage and transport, then released intact when needed for analysis

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

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

Enables the reliable detection and quantification of low-abundance biomarkers, such as human growth hormone in urine, even at low concentrations, improving early disease detection and anti-doping assays with enhanced sensitivity and stability.

Implementation Method 1

The particles are capable of sequestering a biomarker from a mixture based on size and/or affinity of the biomarker for the particle

Methodology Applied
Scientific EffectSize exclusion: Molecular Sieve

Implementation Method 2

The particles are capable of sequestering a biomarker from a mixture based on size and/or affinity of the biomarker for the particle

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 3

degradation of protein biomarkers can occur immediately following the collection of blood or body fluid as a result of endogenous or exogenous proteinases

Methodology Applied
Scientific EffectSequestration: Absorption (physical)

Implementation Method 4

amplify the concentration of low abundance biomarkers in urine

Methodology Applied
Scientific EffectConcentration:

Data Source

PatentUS9383299B2Method for harvesting nanoparticles and sequestering biomarkers
Publication Date: 2016.07.05 CERES NANOSCI
  • US9383299B2 patent drawing
  • US9383299B2 patent drawing
  • US9383299B2 patent drawing

AI summary

Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles are changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles are made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.