Potentiometric Titration for Molecular Interaction Analysis

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Solution Overview

Problem

Current methods for characterizing molecular interactions, such as those between biomolecules and small molecules, are often expensive, time-consuming, and complex, particularly when determining selectivity and sensitivity using potentiometric sensors, where little is known about the selectivity of aptamers and antibodies, especially for small organic molecules.

Innovation Solution

A simple and general potentiometric method using potentiometric titration to derive interaction properties between molecules, involving the transformation of potential signals into concentration-related signals, allowing for accurate detection of binding strengths and association constants, even at low concentrations, using a system with a potentiometric indicator electrode and a reference electrode.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional methods (SPR, ITC, DSC, QMB) are used to study molecular interactions, then measurement precision is improved, but device complexity and cost increase

Engineering Contradiction:
Improveaffinity measurement precisionVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical and optical measurement systems (SPR, QMB) with a simple potentiometric electrochemical system. Instead of using surface plasmon resonance optics or quartz crystal mechanics, the invention uses ion-selective electrodes to measure potential changes during titration, achieving comparable affinity measurements with much simpler equipment

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

Solution Approach 2:

The patent changes the measurement parameter from optical signals (SPR), thermal signals (ITC, DSC), or mechanical frequency (QMB) to electrochemical potential signals. This parameter transformation allows the use of simple potentiometric titration equipment to achieve precise affinity measurements that previously required complex instrumentation

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If concentration-based assays are used to quantify affinity, then measurement precision is improved, but loss of time increases

Engineering Contradiction:
Improveaffinity quantification precisionVSAvoidtitration time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs continuous potentiometric monitoring during titration, where the potential is measured continuously as titrant is added. This continuous measurement approach allows for rapid data collection and immediate determination of binding parameters, reducing the time required compared to discrete sampling methods while maintaining precision

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent uses automated titration systems that rapidly add titrant in controlled increments while continuously monitoring potential. This allows the titration to be completed quickly through automated operation, reducing manual intervention time and accelerating the overall measurement process while maintaining measurement precision

Inventive Principle:
Principle #21Skipping (Rushing through)

3Measurement precision

If biomolecular recognition elements are used in potentiometric sensors, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improvebiomolecule detection precisionVSAvoidsensor construction complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent separates the recognition function from the detection function. The biomolecular recognition element (aptamer or antibody) is isolated as a distinct component that can be independently optimized and characterized, while the potentiometric detection system remains a simple, standardized electrochemical platform. This segmentation allows complex biomolecular functionality to be combined with simple detection equipment

Inventive Principle:
Principle #1Segmentation

4Measurement precision

If selectivity of aptamers and antibodies for small molecules is studied, then measurement precision is improved, but loss of time increases

Engineering Contradiction:
Improveselectivity determination precisionVSAvoidselectivity analysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent develops a universal potentiometric titration platform that can assess selectivity of different biomolecules (aptamers, antibodies) for various small molecule targets using the same simplified methodology. This single platform replaces multiple specialized assays, allowing rapid comparison of selectivity across different biomolecule-analyte pairs without requiring time-consuming method development for each case

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 provides a cost-effective, fast, and accurate means to determine interaction properties between molecules, applicable in various fields like biosensors, molecular biology, and pharmacy, enabling precise analysis of biomolecular interactions beyond the limitations of traditional techniques.

Implementation Method 1

obtaining potentiometric titration results for a potentiometric measurement during titration of a solution with a titrant

Methodology Applied
Scientific EffectPotentiometry: Electric Field

Data Source

PatentUS11614423B2Transformed response potentiometric titrations
Publication Date: 2023.03.28 UNIVERSITEIT ANTWERPEN
  • US11614423B2 patent drawing
  • US11614423B2 patent drawing
  • US11614423B2 patent drawing

AI summary

The present invention relates to a method and system for obtaining an interaction property between a molecule or biomolecule or particle or bioparticle or nano- or microparticle on the one hand and a target particle on the other hand. The method comprises obtaining potentiometric titration results for a potentiometric measurement during titration of a solution with a titrant, said solution being a solution of one of a ligand of the target particle or said molecule or biomolecule or particle or bioparticle or nano- or microparticle. Said titrant comprises the other of said target particle ligand or said molecule or biomolecule or particle or bioparticle or nano- or microparticle. The method also comprises deriving based on said potentiometric titration results an interaction property between said molecule or biomolecule or particle or bioparticle or nano- or microparticle and said target particle.