Biomolecule Assay Enrichment Using pH-Tuned Selective Adsorption
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Solution Overview
Problem
Biological samples, such as biofluids, contain a wide variety of proteins that overshadow the signals of other proteins in assays, and sample preparation methods like dilution can further obscure relative signals.
Innovation Solution
A method involving the selective enrichment of different biomolecule types in fluid compositions with varying pH, ionic strength, temperature, and other intensive physical properties, followed by adsorption onto surfaces with specific charge and functional groups, and subsequent washing, purifying, and reconstituting steps to enhance the detection of low-abundance biomolecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high abundance proteins are present in biological samples, then the sample contains comprehensive protein information, but the high abundance proteins overshadow the signal of low abundance proteins making them undetectable
Solution Approach 1:
The patent divides the protein enrichment process into multiple sequential steps using different particle types with distinct surface properties. Each particle type selectively enriches specific protein subsets based on their unique characteristics, thereby segmenting the overwhelming protein mixture into manageable, detectable groups.
Solution Approach 2:
Different particle types are assigned different surface properties (charge, hydrophobicity, functional groups) that create localized selective environments. Each particle type's surface is optimized for binding specific protein characteristics, enabling selective enrichment of low abundance proteins while high abundance proteins are enriched by different particle types in subsequent steps.
2Quantity of substance
If sample dilution is performed to reduce high abundance protein signals, then the dynamic range is compressed, but the relative signals of proteins are further obscured
Solution Approach 1:
The patent changes multiple parameters of the fluid composition including pH, ionic strength, temperature, and solvent composition to optimize protein-particle interactions. These parameter changes enhance the selective binding of specific protein subsets to different particle types, improving detection sensitivity without requiring sample dilution.
3Adaptability or versatility
If multiple particle types with different surface properties are used for selective enrichment, then different protein subsets can be enriched, but the device complexity increases
Solution Approach 1:
The patent combines multiple particle types with different surface properties into a single mixed particle composition that can be used together in one assay. This merging approach allows simultaneous or sequential enrichment of different protein subsets using multiple particle types without requiring separate complex procedures for each particle type.
Solution Approach 2:
The different particle types in the composition serve multiple functions: each particle type selectively binds specific protein subsets based on their unique surface properties, and together they provide comprehensive protein coverage. The mixed particle composition acts as a universal enrichment system that handles diverse protein types through a single standardized assay protocol.
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
Enhances the detection of low-abundance biomolecules by increasing the dynamic range and reducing variance, allowing for more accurate identification of proteins and peptides in complex biological samples.
Implementation Method 1
selectively enriching a first plurality of biomolecule types in a first fluid composition; selectively enriching a second plurality of biomolecule types in a second fluid composition
Data Source
AI summary
In some aspects, the present disclosure provides a method comprising: (a) selectively enriching a first plurality of biomolecule types in a first fluid composition; (b) selectively enriching a second plurality of biomolecule types in a second fluid composition; and (c) performing a downstream assay on biomolecule types of the first plurality of biomolecule types and the second plurality of biomolecule types, wherein the first fluid composition comprises a first pH, and the second fluid composition comprises a second pH, wherein the first pH and the second pH are different or the same. Also disclosed are systems, kits, compositions, and computer-readable media for performing biomolecule assays.