Bioreactor Analyte Monitoring via Automated Sampling and Chromatography

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Solution Overview

Problem

Current methods for real-time analysis of analyte concentrations in fermentation bioreactors are limited by the need for sterility, which restricts sampling and data collection, and can only measure high nutrient levels at the beginning of a batch, leading to information gaps and inability to measure analyte levels when concentrations are low.

Innovation Solution

A self-contained, automated system for direct real-time measurement of analyte concentrations using a growth vessel, sampling system, filtration, affinity chromatography, and optical detection, capable of measuring throughout the fermentation process with low detection limits and correction for buffer background, allowing continuous monitoring of biologics and nutrient levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If real-time sampling is performed to measure analyte concentrations throughout fermentation, then measurement capability is improved, but sterility is compromised and foreign cell/pathogen growth occurs

Engineering Contradiction:

Improveanalyte concentration measurementVSAvoidforeign cell or pathogen growth

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces an intermediary sampling system that takes samples from the bioreactor through a controlled sampling port, allowing measurement without direct penetration of the sterile reactor environment. The sampling system acts as a mediator that bridges the sterile interior and non-sterile measurement equipment, maintaining sterility while enabling real-time analysis.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If sampling and data generation time is reduced to achieve real-time measurement, then productivity is improved, but measurement accuracy deteriorates due to insufficient data processing time

Engineering Contradiction:

Improvereal-time data generation speedVSAvoiddata accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The system performs self-service by automatically executing the complete measurement workflow including sampling, filtration, chromatography separation, detection, and data processing without manual intervention. This automation enables real-time measurements while maintaining accuracy through consistent, repeatable automated operations.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent replaces manual mechanical sampling and laboratory analysis procedures with an automated system that uses electronic controls, computer-generated workflows, and integrated instrumentation. This substitution enables rapid, real-time measurements while maintaining or improving measurement accuracy through precise electronic control.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Object-affected harmful factors

If current measurement devices are used to maintain sterility, then sterility is preserved, but measurement capability is limited to high concentrations only

Engineering Contradiction:

Improvesterility maintenanceVSAvoidmeasurement concentration range

Core Design Contradiction:

Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The system changes the operational parameters of the measurement process by using affinity chromatography with optimized flow rates, detection sensitivities, and sample processing conditions that enable accurate measurement across the full concentration range from trace levels to high concentrations, all while maintaining sterility.

Inventive Principle:

Principle #35Parameter changes

4Measurement precision

If nutrient levels are measured only at the beginning of the batch when concentrations are high, then measurement accuracy is maintained, but information gaps occur during the fermentation process

Engineering Contradiction:

Improvenutrient level measurementVSAvoidfermentation process data

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The system establishes continuous measurement capability throughout the entire fermentation process by automatically sampling and analyzing analyte concentrations at multiple time points. This continuous monitoring eliminates information gaps and provides real-time data on nutrient levels, analyte production, and fermentation progress from start to finish.

Inventive Principle:

Principle #20Continuity of useful action

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

Enables accurate, continuous monitoring of biologic and nutrient concentrations from start to finish of the fermentation process, reducing information gaps and enabling timely adjustments to maintain optimal production parameters, even at low analyte levels.

Implementation Method 1

removing and loading analyte or analytes onto a cartridge with affinity chromatography stationary phase

Methodology Applied

Scientific EffectAffinity chromatography: Chromatography

Implementation Method 2

an optical detector

Methodology Applied

Scientific EffectOptical detection: Absorption Spectroscopy

Data Source

PatentUS10585095B2Systems and methods for bioprocess analysis

Publication Date: 2020.03.10 CIRCLE TECH

AI summary

Disclosed herein are systems, methods, and devices for monitoring and controlling bioprocess parameters. The systems and methods enable automated operation with real-time analysis of process conditions and analyte or biologic production.