Inline Buffer Dilution Control Using Pre-Dilution pH Measurement

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Solution Overview

Problem

Existing inline buffer dilution systems suffer from inaccurate sensor measurements, particularly at low concentrations, due to the degradation or slowdown of sensor performance when mixing low-concentration buffers with diluents.

Innovation Solution

The system measures the pH of a small quantity of high-concentration buffer solution before dilution, using a central controller to control flow controllers and mixers to ensure accurate pH measurement, followed by dilution with a diluent, thereby maintaining pH accuracy in the final diluted solution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If sensors are placed inline to measure buffer solution characteristics, then real-time measurement capability is improved, but measurement precision deteriorates at low concentrations due to sensor degradation

Engineering Contradiction:
Improvemeasurement time delayVSAvoidpH measurement accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The system performs preliminary measurement of the concentrated buffer solution before dilution occurs. By measuring the pH of the undiluted buffer solution upstream of the dilution point, the system captures accurate sensor readings when the buffer concentration is high and sensor performance is optimal. The control system then uses this preliminary measurement data to adjust dilution rates and achieve the desired final pH, eliminating the need to measure after dilution when sensor accuracy deteriorates.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If dilution is performed immediately after mixing buffers, then productivity is improved, but measurement precision worsens due to low concentration effects

Engineering Contradiction:
Improvebuffer production rateVSAvoidpH measurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system measures pH before dilution to establish baseline data, then performs dilution at high speed using this pre-established information. The control system calculates the required dilution amount based on the preliminary measurement and executes the dilution rapidly, maintaining both high productivity and measurement precision by decoupling the measurement timing from the dilution timing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system implements a feedback control loop where preliminary pH measurements inform dilution control decisions. The control system continuously monitors the preliminary measurements and adjusts dilution rates in real-time to achieve target pH values, enabling fast dilution operations while maintaining accuracy through closed-loop control based on pre-dilution measurement data.

Inventive Principle:
Principle #23Feedback

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 system achieves more accurate pH measurements in the diluted buffer solution, with a maximum difference of 0.33 pH units from the actual value, ensuring closer alignment with desired pH levels.

Implementation Method 1

a first mixer fluidly connected to the first and second flow control mechanism and configured to receive an amount of first buffer fluid via the first flow controller and second buffer fluid via the second flow controller, the first mixer further configured to mix the amount of the first buffer fluid and the second buffer fluid

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

a first mixer fluidly connected to the first and second flow control mechanism and configured to receive an amount of first buffer fluid via the first flow controller and second buffer fluid via the second flow controller, the first mixer further configured to mix the amount of the first buffer fluid and the second buffer fluid

Methodology Applied
Scientific EffectConvection: Convection

Implementation Method 3

a series of sensors fluidly connected to the first mixer and configured to receive the buffer solution from the first mixer, the sensors configured to measure characteristics of the buffer solution

Methodology Applied
Scientific EffectElectrochemical measurement:

Implementation Method 4

a second mixer fluidly connected to the series of sensors and the third flow controller, the second mixer configured to receive the buffer solution via the series of sensors and an amount of diluent fluid via the third flow controller, the second mixer further configured to mix the buffer solution and the amount of diluent fluid

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 5

a second mixer fluidly connected to the series of sensors and the third flow controller, the second mixer configured to receive the buffer solution via the series of sensors and an amount of diluent fluid via the third flow controller, the second mixer further configured to mix the buffer solution and the amount of diluent fluid

Methodology Applied
Scientific EffectConvection: Convection

Data Source

PatentUS20260072052A1Buffer Dilution System That Provides More Accurate Inline Measurements
Publication Date: 2026.03.12 ASAHI KASEI BIOPROCESS AMERICA INC
  • US20260072052A1 patent drawing
  • US20260072052A1 patent drawing
  • US20260072052A1 patent drawing

AI summary

An inline buffer dilution system is provided that includes a first flow controller fluidly connected to a supply of a first buffer, a second flow controller fluidly connected to a supply of a second buffer, and a first mixer fluidly connected to the first and second flow controllers and configured to mix an amount of the first buffer and the second buffer to produce a buffer solution. Characteristics of this solution are measured through a series of sensors before the buffer solution is diluted in a mixer, in which a third flow controller fluidly connected to a supply of diluent is fluidly connected to the mixer. The system further includes a central controller configured to control the release of the diluent liquid, the first buffer, and the second buffer being mixed in the first mixer, such that diluted buffer solution meets certain target characteristics.