In Situ Sensor Calibration via Sterile Fluid Delivery

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Solution Overview

Problem

Current sensor technologies used in bioprocess monitoring within bioreactors require periodic calibration, which is challenging due to the risk of contamination when removing sensors from sterile environments, and often necessitates off-line sample analysis.

Innovation Solution

A measurement system and method for in situ calibration of sensors, which includes a housing with a culture medium, a measurement probe with a sensor and channel, and a calibration unit that supplies a calibration fluid through the channel to the sensor, allowing for calibration without removing the sensor from the bioreactor.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sensors are removed from bioreactors for calibration, then calibration can be performed, but sterility is compromised and contamination risk increases

Engineering Contradiction:
Improvesensor calibration accuracyVSAvoidsterility maintenance
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

A sterile adapter is introduced as an intermediary component between the sensor and the calibration system. The adapter includes a sterile barrier that prevents contamination while allowing calibration fluid to reach the sensor through a controlled interface, thus maintaining sterility during calibration operations

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system is divided into separate sterile and non-sterile zones using the adapter assembly. The sensor remains in the sterile zone within the bioreactor, while the calibration fluid delivery mechanism operates in a non-sterile zone, with the sterile barrier creating a controlled interface between these zones

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If off-line sample analysis is used for sensor correction, then calibration can be achieved, but additional analytical facilities and skilled personnel are required

Engineering Contradiction:
Improvesensor reading accuracyVSAvoidanalytical facility requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The sensor calibration is performed in-situ within the bioreactor using the calibration fluid delivery system, eliminating the need for external analytical facilities. The system self-calibrates by directly exposing the sensor to known calibration concentrations without requiring separate analysis equipment or specialized personnel

Inventive Principle:
Principle #25Self-service

3Duration of action of moving object

If sensors operate for extended periods in bioreactors, then continuous monitoring is achieved, but calibration accuracy deteriorates over time

Engineering Contradiction:
Improvesensor operational durationVSAvoidmeasurement accuracy
Core Design Contradiction:
Duration of action of moving objectVSMeasurement precision

Solution Approach 1:

The calibration fluid delivery system enables continuous or periodic calibration of the sensor while it operates in the bioreactor. The sterile adapter allows repeated calibration operations without removing the sensor, maintaining continuous monitoring capability while periodically restoring measurement accuracy

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

Calibration is performed periodically at predetermined intervals during sensor operation. The system proactively recalibrates the sensor before significant drift occurs, ensuring measurement accuracy is maintained throughout the extended operational period

Inventive Principle:
Principle #10Preliminary 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 and sterile in situ calibration of sensors, preventing contamination and reducing the need for off-line sample analysis, thereby improving measurement reliability and efficiency in bioprocess monitoring.

Implementation Method 1

A rapid diffusion and dilution of the calibration fluid into the culture medium may be prevented

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

the at least one measurement probe comprises a membrane encompassing the at least one sensor, configured to confine the calibration fluid at or around the at least one sensor

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Data Source

PatentUS20250154447A1Measurement System and Method for in Situ Calibration
Publication Date: 2025.05.15 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • US20250154447A1 patent drawing
  • US20250154447A1 patent drawing
  • US20250154447A1 patent drawing

AI summary

A measurement system is provided for in situ calibration. The measurement system includes a housing including a culture medium and measurement probe arranged in the culture medium. The measurement probe includes an opening, a sensor, and a channel arranged from the opening to the sensor. The measurement system further includes a calibration unit connected to the opening and configured to supply a calibration fluid to the sensor via the channel.