Monolithic Flow Cell Assembly for UV-Vis Bioprocess Monitoring

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Solution Overview

Problem

Current bioprocessing technologies lack integration of broadband ultraviolet-visible (UV-Vis) spectroscopy and other spectroscopic techniques into downstream processing, particularly in single-use equipment, due to alignment challenges and complexity with moving parts, limiting on-line and in-line measurements and calibration capabilities.

Innovation Solution

A flow cell assembly with a monolithic glass body and precise optical path length, allowing for on-line and in-line monitoring of bioprocess parameters without alignment issues, using a universal glass body that can be used across different scales and applications, integrated into the process flow path to minimize measurement uncertainties and facilitate real-time monitoring.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a moving fiber is used to vary optical path length, then a broad linear range for protein detection is achieved, but the alignment becomes time-consuming and complex

Engineering Contradiction:
Improvelinear range for protein detectionVSAvoidalignment time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the alignment problem by using a fixed fiber position and instead varies the optical path length by moving the flow cell assembly relative to the fiber. This transfers the movement from the fiber (which requires precise alignment) to the flow cell (which can be moved without affecting alignment), thereby resolving the time-consuming alignment issue while maintaining the ability to vary optical path length for broad linear range detection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of moving the fiber to change optical path length (conventional approach), the patent inverts the approach by moving the flow cell assembly while keeping the fiber stationary. This inversion eliminates the alignment problem because the stationary fiber maintains its precise position, while the movable flow cell provides the necessary optical path length variation.

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

2Adaptability or versatility

If a moving fiber is used to vary optical path length, then broadband spectroscopy measurement range is expanded, but the device complexity increases due to moving parts

Engineering Contradiction:
Improvespectroscopy measurement rangeVSAvoidmoving parts
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent removes the moving fiber component entirely and extracts only the essential function of varying optical path length. By using a stationary fiber and moving the flow cell assembly instead, the design eliminates complex alignment mechanisms while maintaining the ability to perform broadband spectroscopy measurements across a range of optical path lengths.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The flow cell assembly is designed as a disposable single-use component that can be easily replaced. This eliminates the need for complex, expensive alignment mechanisms and moving parts, as each new flow cell is pre-positioned and requires no alignment. The disposable nature simplifies the overall device complexity while maintaining measurement versatility.

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

3Measurement precision

If fiber alignment is performed with high accuracy, then measurement precision is improved, but the ease of operation deteriorates

Engineering Contradiction:
Improvealignment accuracyVSAvoidalignment process
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The fiber is pre-aligned and fixed in a stationary position before use. The flow cell assembly is designed with pre-marked positioning features that guide its placement relative to the fiber. This preliminary alignment action eliminates the need for operators to perform complex alignment procedures during operation, thereby maintaining high measurement precision while dramatically improving ease of operation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The flow cell assembly incorporates self-aligning features such as positioning marks and geometric constraints that automatically guide its correct placement relative to the stationary fiber. This self-service alignment mechanism eliminates the need for operator intervention in the alignment process, maintaining precision while simplifying operation to a simple plug-and-play procedure.

Inventive Principle:
Principle #25Self-service

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 efficient, real-time monitoring of bioprocess parameters without disrupting the flow, reducing shear stress on cells and allowing for precise spectral analysis and calibration, applicable in both downstream and upstream processes, including single-use equipment.

Implementation Method 1

Absorbance is determined as the ratio of the light applied from the source to the light after interaction with the sample (transmission or reflection measurement)

Methodology Applied
Scientific EffectAbsorbance: Absorption (EM radiation)

Data Source

PatentUS20230168179A1Flow cell assembly and spectroscopy device assembly for use in a bioprocess
Publication Date: 2023.06.01 SARTORIUS STEDIM BIOTECH GMBH
  • US20230168179A1 patent drawing
  • US20230168179A1 patent drawing
  • US20230168179A1 patent drawing

AI summary

A flow cell assembly for use in a bioprocess including a housing and a glass body. The housing includes an inlet tube connector and an outlet tube connector and a holding structure for immovably holding the glass body. The glass body is a universal single-piece glass body surrounding a measurement channel. The measurement channel has an inlet end and an outlet end defining a medium flow direction, and a defined dimension along an optical measurement axis perpendicular to the medium flow direction. The inlet end and outlet end of the measurement channel are in fluid communication with the inlet tube connector and the outlet tube connector of the housing, respectively. The housing or the glass body includes an aligning structure for aligning a probe head. The housing or the glass body includes a fixing structure for immovably fixing the aligned probe head relative to the glass body.