Reusable Raman Probe Assembly for Single-Use Bioreactors

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Solution Overview

Problem

Existing Raman spectroscopy systems struggle to achieve precise and repeatable sampling in single-use bioreactor vessels due to the trade-off between the expense and complexity of Raman probes and the disposable nature of bioreactor bag assemblies, which limits accuracy and reaction model transferability between batches.

Innovation Solution

A Raman probe assembly that combines reusable and disposable components, featuring a high-precision window sealed in a disposable barb with an optic component containing focusing lenses, utilizing an adjustable spacer and alignment tooling to set the focus at a precise depth within the bioreactor medium, ensuring accurate and cost-effective sampling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a sophisticated fiber-optic coupled Raman probe is used for process sampling, then measurement precision is improved, but device complexity and cost increase

Engineering Contradiction:
ImproveRaman sampling accuracyVSAvoidprobe complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system is divided into a reusable Raman probe head and a disposable port assembly with integrated optics. This segmentation allows the complex probe to be separated from the disposable components, maintaining measurement precision while reducing overall system complexity through modular design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A disposable port assembly with integrated window and coupling components serves as an intermediary between the Raman probe and the bioreactor bag. This intermediary enables precise optical coupling without requiring the probe itself to be disposable, thus maintaining measurement accuracy while simplifying the reusable probe design.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If a disposable bioreactor bag assembly is used, then ease of manufacture and cost are improved, but measurement precision deteriorates due to alignment difficulties

Engineering Contradiction:
Improvebioreactor vessel cost-effectivenessVSAvoidRaman sampling accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The optical components (window, lens, fiber coupling) are pre-assembled and pre-aligned in the disposable port assembly before insertion into the bioreactor. This preliminary alignment ensures that when the probe is connected, precise optical coupling is achieved without requiring complex alignment procedures during use, thus maintaining measurement precision while using disposable components.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The port assembly with integrated optical components is designed as a disposable component that is inexpensive to manufacture. By concentrating the precision requirements in the reusable probe head and using a simple disposable interface, the system achieves accurate measurements while keeping the disposable portion cost-effective.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Length of moving object

If the Raman probe focus is set too deep into the turbid sample, then sampling depth is improved, but measurement precision deteriorates due to spectrum distortion

Engineering Contradiction:
Improvefocus depthVSAvoidRaman spectrum accuracy
Core Design Contradiction:
Length of moving objectVSMeasurement precision

Solution Approach 1:

The optical design parameters (lens focal length, window thickness, fiber positioning) are specifically optimized to achieve the correct focus depth in turbid media. By carefully selecting and adjusting these parameters in the disposable port assembly, the system achieves optimal focus at the desired depth while maintaining spectrum accuracy and avoiding distortion.

Inventive Principle:
Principle #35Parameter changes

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 sophisticated Raman sampling with disposable bioreactor vessels while maintaining precision and reducing costs, ensuring consistent results from batch to batch and probe to probe without compromising sampling accuracy.

Implementation Method 1

a lens for focusing light to, and collecting light from, a sample focus in the reaction medium

Methodology Applied
Scientific EffectLight focusing: Lens

Implementation Method 2

Raman spectroscopy has become a powerful tool for use in conjunction with in situ process analysis

Methodology Applied
Scientific EffectRaman scattering: Rayleigh Scattering

Data Source

PatentEP3566030B1Cost-effective raman probe assembly for single-use bioreactor vessels
Publication Date: 2021.06.30 KAISER OPTICAL SYST INC
  • EP3566030B1 patent drawingFigure 1A
  • EP3566030B1 patent drawingFigure 1B~2C
  • EP3566030B1 patent drawingFigure 3A~3B

AI summary

Systems and methods are used to couple an optical sampling probe to a port in a single-use bioreactor bag for in-process monitoring. A combination of re-useable and disposable components maintain precision while reducing costs. A disposable barb with an integral window, received by the port of the reaction vessel, is coupled to a re-useable optic component with a focusing lens. A separate focus alignment tool is used to set the lens position to a precise focal point before placement of the optic component into the barb. The fixture includes a window to simulate the window in a barb component, a target with a known spectral signature, and a probe head coupled to a spectral analyzer. The axial position of the lens is adjusted with respect to the spacer component to maximize the spectral signature from a sample target, whereupon the spacer component is bonded to the lens mount.