Bioreactor Permittivity Analysis via Physics-Based Model

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Solution Overview

Problem

Current bioreactor analytical tools face challenges in providing direct measurements of cell parameters like viable cell density and glucose concentration, requiring complex calibration models and large datasets, especially when scaling up from small to large bioreactors.

Innovation Solution

A computer-supported physics-based model is used to analyze biomass in bioreactors, converting real-time raw data from sensors into specific cell parameters, such as radius and viable cell density, without the need for extensive data-driven calibration or machine learning.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If data-driven calibration models are used for PAT sensors, then measurement accuracy can be achieved, but the complexity of calibration increases significantly requiring multiple cell culture runs and large datasets

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidcalibration complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the calibration requirement from the measurement process by using a physics-based model that inherently accounts for sensor characteristics. The model separates the physical measurement principles from the specific sensor implementation, allowing direct calculation of cell parameters without extensive calibration data collection

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary characterization of cell properties (membrane capacitance, internal conductivity) through offline measurements before the main measurement process. This preliminary action enables the physics-based model to directly compute cell parameters from raw sensor signals without requiring multiple calibration runs

Inventive Principle:
Principle #10Preliminary action

2Productivity

If multi-use sensors are converted to single-use sensors, then cleaning steps are eliminated and system downtime is reduced, but calibration becomes significantly more difficult

Engineering Contradiction:
Improvesystem availabilityVSAvoidcalibration ease
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The physics-based model enables single-use sensors to self-characterize by using the sensor's own raw measurement signals in combination with cell property parameters. The sensor does not require external calibration procedures but can directly provide quantitative cell parameters through the physics-based calculation model

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent changes the approach from calibration-based parameter adjustment to physics-based parameter calculation. By using fundamental physical relationships and cell property parameters, the system eliminates the need for calibration procedures while maintaining measurement accuracy for single-use sensors

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If data-driven calibration models are used for PAT sensors, then parameter measurements can be obtained, but the models cannot be transferred between different sensors or bioreactor scales

Engineering Contradiction:
Improveparameter measurement capabilityVSAvoidmodel transferability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The physics-based model provides a universal framework that can be applied across different sensor types, bioreactor scales, and cell culture conditions. The model uses fundamental physical principles and cell property parameters that are invariant across different implementations, enabling broad applicability without re-calibration

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

Solution Approach 2:

Instead of adapting the model to each specific sensor through calibration, the patent inverts the approach by using the sensor's raw signals as input to a universal physics-based model. This allows the same model structure to work with different sensors and scales without requiring sensor-specific calibration data

Inventive Principle:
Principle #13The other way round (Inversion)

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 approach allows for real-time, accurate measurement of cell parameters across various bioreactor sizes, reducing calibration efforts and enabling seamless transition between multi-use and single-use sensors, thus improving process efficiency and scalability.

Implementation Method 1

a capacitance probe integrating the dielectric spectroscopy... the dielectric spectroscopy gives quantitative media permittivity data

Methodology Applied
Scientific EffectDielectric spectroscopy: Dielectric Permittivity

Data Source

PatentUS20250043232A1Model-based analytical tool for bioreactors
Publication Date: 2025.02.06 MERCK PATENT GMBH
  • US20250043232A1 patent drawing
  • US20250043232A1 patent drawing
  • US20250043232A1 patent drawing

AI summary

Method and system to analyze biomasses in a bioreactor (3) via a computer (2) with a system software (5), the bioreactor (3) having at least one sensor (6) to measure the biomasses and which has a data connection to the computer (2) managed by a data interface provided by the system software (5), wherein the system software (5) provides a data conversion model (8) to analyze real time raw data about permittivity measured by and transmitted from the at least one sensor (6) to the computer (2) to calculate specific cell parameters of cells in the biomasses.