Core-shell hydrogel particles for biomarker harvesting

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Solution Overview

Problem

Current methods for biomarker detection in blood are hindered by the low abundance and rapid degradation of biomarkers, which are masked by high-abundance proteins and susceptible to enzymatic degradation, making early disease detection challenging.

Innovation Solution

Development of core-shell hydrogel particles that selectively capture and concentrate low-abundance biomarkers, protecting them from degradation and allowing for their subsequent analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods (two-dimensional gel electrophoresis, mass spectrometry) are used for biomarker detection, then high-abundance proteins can be detected, but low-abundance biomarkers are masked and cannot be detected

Engineering Contradiction:
Improvedetection sensitivity for low-abundance biomarkersVSAvoidconcentration of high-abundance proteins masking biomarkers
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention segments the complex biological fluid into different components by size using porous particles. The porous structure allows small biomarkers to enter while excluding large proteins, effectively segmenting the mixture based on molecular size to enable detection of low-abundance biomarkers that would otherwise be masked.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The porous particles provide a localized environment with specific pore sizes that create different quality conditions for different molecules. The pore structure creates a selective local environment that favors the capture and concentration of small biomarkers while excluding large proteins, enabling precise detection of low-abundance species.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If blood samples are collected for biomarker analysis, then biomarkers can be detected, but rapid degradation by endogenous or exogenous proteinases occurs immediately following collection

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidstability of biomarkers after sample collection
Core Design Contradiction:
Measurement precisionVSDuration of action of moving object

Solution Approach 1:

The invention performs preliminary action by capturing and concentrating biomarkers into porous particles immediately upon sample collection, before degradation can occur. This preliminary capture stabilizes the biomarkers in a protected state, preventing subsequent degradation by proteinases and preserving the sample for later analysis.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The porous particles act as an intermediary between the biomarkers and the degrading proteinases. The particles capture and sequester biomarkers within their porous structure, creating a physical barrier that prevents proteinases from accessing and degrading the captured biomarkers, thus stabilizing them for extended periods.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If high-abundance proteins are depleted using immunoaffinity depletion columns, then low-abundance biomarkers become more detectable, but the yield of candidate biomarkers is significantly reduced

Engineering Contradiction:
Improvedetectability of low-abundance biomarkersVSAvoidyield of candidate biomarkers
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention uses porous particles with specifically engineered pore sizes to selectively capture low-abundance biomarkers while allowing high-abundance proteins to pass through. This porous material approach enables direct enrichment of biomarkers without the need for depletion steps, preserving the complete biomarker pool including those associated with carrier proteins.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

Instead of removing high-abundance proteins to make biomarkers detectable (the conventional depletion approach), the invention inverts the strategy by directly capturing and concentrating the low-abundance biomarkers themselves. This inversion preserves the natural associations between biomarkers and carrier proteins, maintaining higher yields of candidate biomarkers.

Inventive Principle:
Principle #13The other way round (Inversion)

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 particles effectively harvest, concentrate, and stabilize low-abundance biomarkers, enabling their detection and analysis, even in complex biological mixtures, thereby facilitating early disease detection and diagnosis.

Implementation Method 1

core-shell hydrogel particles that selectively capture and concentrate low-abundance biomarkers

Methodology Applied
Scientific EffectSelective binding: Adsorption

Implementation Method 2

protecting them from degradation

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Data Source

PatentUS8497137B2Smart hydrogel particles for biomarker harvesting
Publication Date: 2013.07.30 INST SUPERIORE DI SANITA
  • US8497137B2 patent drawing
  • US8497137B2 patent drawing
  • US8497137B2 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.