Buffer pH Preparation Using Additive-Corrected ΔpH Modeling

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Solution Overview

Problem

Existing methods for preparing buffer solutions of specific pH are unreliable due to discrepancies between theoretical and actual pH values, especially when considering the effects of additives such as salts, chaotropes, chelating agents, and surfactants, making it impractical to store ready-made solutions and requiring improved calculation methods.

Innovation Solution

A method involving the calculation of theoretical acid and base concentrations using the Henderson-Hasselbalch equation combined with the Debye Huckel theory, followed by experimental measurement and generation of a mathematical model to correct for pH differences (ΔpH) across various additive concentrations, allowing for precise adjustment of acid and base concentrations to achieve the desired pH.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If theoretical pH calculations using Henderson-Hasselbalch equation and Debye Huckel theory are used, then the preparation process is simple and straightforward, but the actual pH achieved does not correspond with the theoretical pH, especially when additives are present

Engineering Contradiction:
Improvesimplicity of preparation processVSAvoidaccuracy of pH value
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by pre-determining correction factors (ΔpH values) through theoretical calculations using the Henderson-Hasselbalch equation combined with the Debye-Hückel theory for various additive concentrations. These correction factors are calculated in advance and stored in a lookup table, allowing the actual pH to be accurately predicted and adjusted without complex real-time measurements or iterations during buffer preparation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the need for iterative experimental pH adjustment (mechanical/physical trial-and-error process) with a computational approach. By substituting the mechanical adjustment process with theoretical calculations and correction factor application, the method achieves accurate pH prediction and preparation through mathematical computation rather than physical experimentation and adjustment.

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

2Manufacturing precision

If ready-made buffer solutions are stored for various compositions and pH values, then accurate pH values can be obtained, but logistical storage requirements become impractical

Engineering Contradiction:
Improveaccuracy of pH valueVSAvoidlogistical storage requirements
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent creates a computational model (mathematical representation) that copies and simulates the behavior of buffer solutions across different compositions and pH values. Instead of physically storing multiple ready-made buffer solutions, the method uses a lookup table containing pre-calculated correction factors that replicate the pH behavior of buffers with various additives, enabling accurate pH preparation through calculation rather than physical storage.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent enables flexible buffer preparation by allowing users to input different additive concentrations and buffer compositions as parameters. The system then retrieves or calculates the appropriate correction factor for those specific parameters, enabling the preparation of accurate buffer solutions with varying compositions without requiring physical storage of each possible buffer variant.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If standard Henderson-Hasselbalch equation is used without correction factors, then calculations are straightforward, but the pH accuracy deteriorates due to ion size, charge, temperature, and additive effects

Engineering Contradiction:
Improvesimplicity of calculationVSAvoidpH value accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent introduces correction factors (ΔpH values) as an intermediary element between the simple Henderson-Hasselbalch calculation and the actual pH value. These correction factors account for the effects of ion size, charge, temperature, and additives without requiring complex modifications to the original equation. The intermediary correction factor bridges the gap between simple calculation and accurate pH prediction.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent segments the pH calculation process into two distinct parts: (1) the base Henderson-Hasselbalch calculation that provides the theoretical pH, and (2) the additive correction factor that adjusts for real-world deviations. This segmentation allows the user to maintain the simplicity of the original equation while systematically accounting for various influencing factors through separate correction terms.

Inventive Principle:
Principle #1Segmentation

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 ensures high accuracy in achieving the target pH within ±0.1 units, as demonstrated by examples with phosphate and acetate buffers, enabling the preparation of reliable buffer solutions for biomolecule processing and other applications.

Implementation Method 1

calculating the theoretical concentrations of acid and base for the solution to have the defined pH using the Henderson-Hasselbach equation in combination with the Debye Huckel theory

Methodology Applied
Scientific EffectHenderson-Hasselbalch equation:

Implementation Method 2

calculating the theoretical concentrations of acid and base for the solution to have the defined pH using the Henderson-Hasselbach equation in combination with the Debye Huckel theory

Methodology Applied
Scientific EffectDebye Huckel theory:

Data Source

PatentUS11911712B2Method for preparing aqueous solutions of a defined pH
Publication Date: 2024.02.27 FUJIFILM DIOSYNTH BIOTECH UK

AI summary

A method for preparing an aqueous solution of a defined pH comprising an acid, a base and optionally one or more additives is provided. The method comprises the steps of:a) calculating the theoretical concentrations of acid and base for the solution to have the defined pH using the Henderson-Hasselbach equation in combination with the Debye Huckel theory for a range of different additive concentrations; b) preparing a sample of the buffer for the range of additive concentrations and measuring the actual pH for each additive concentration; c) calculating a value for delta pH, ΔpH, being the difference between the theoretical pH and the actual pH, for each additive concentration; d) generating a mathematical model describing the relationship of ΔpH with additive concentration; e) selecting the defined pH and additive concentrations; f) using the mathematical model generated in step d) to calculate ΔpH for the defined pH and additive concentration; g) calculating a ΔpH-corrected pH by summing the defined pH and delta pH; h) using the ΔpH-corrected pH to calculate the concentrations of acid and base using the Henderson-Hasselbach equation in combination with the Debye Huckel theory; i) preparing the solution using the concentrations calculated in step h).