Plug Flow Reactor Homogenization for Variable Feed Streams

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Solution Overview

Problem

Existing bioprocessing methods for continuous viral inactivation (CVI) after chromatographic purification steps face challenges with non-uniform feed streams, leading to variable protein concentration and viscosity, which affect downstream processes due to the use of surge vessels, open circuit homogenization loops, and tank-less holds that fail to achieve homogenization, complicating sanitization and troubleshooting.

Innovation Solution

A device and method utilizing a plug flow reactor (PFR) with a bypass line and pumps for in-line homogenization, employing co-current or counter-current flow to circulate the feed stream, reducing concentration differences and achieving uniformity by circulating the feed stream through a closed-circuit flow path.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If surge vessels or open circuit homogenization loops are used to homogenize feed stream, then mixing is achieved, but system sanitization becomes difficult due to product retention

Engineering Contradiction:
Improvefeed stream homogeneityVSAvoidsystem sanitization
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The invention extracts the homogenization function from traditional surge vessels and open circuit loops, implementing it instead within a closed-circuit PFR system where the feed stream is recirculated through the reactor. This extraction allows homogenization to occur without product retention in external vessels, enabling complete system sanitization while maintaining feed stream homogeneity.

Inventive Principle:
Principle #2Taking out (Extraction)

2Manufacturing precision

If bind-and-elute column chromatography is used for purification, then product purification is achieved, but the eluted feed stream has variable concentration (asymmetric Gaussian curve) affecting downstream processes

Engineering Contradiction:
Improveproduct purificationVSAvoidfeed stream concentration uniformity
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The invention applies preliminary homogenization action by recirculating the feed stream through the PFR before it enters downstream processing. The bypass line allows portion of the feed to be mixed with recirculated stream, preliminarily uniformizing the concentration profile (dampening the asymmetric Gaussian curve) to ensure stable input for subsequent viral inactivation or other downstream steps.

Inventive Principle:
Principle #10Preliminary action

3Stability of the object's composition

If recycling feed stream is used for homogenization, then mixing is improved, but flow rate during recycle must be 90 times faster than incubation step which is not ideal for scaling

Engineering Contradiction:
Improvefeed stream homogeneityVSAvoidscaling capability
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The invention applies partial recirculation through the bypass line, where only a portion of the feed stream is diverted for mixing with the main recirculated flow. This partial action achieves effective homogenization without requiring excessive flow rates, making the system scalable. The bypass ratio can be optimized to balance mixing efficiency with acceptable flow rates for industrial scaling.

Inventive Principle:
Principle #16Partial or excessive 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

The PFR system effectively dampens peak concentrations by 70-90% and ensures rapid, efficient homogenization of non-uniform feed streams, facilitating easier sanitization and reducing operational complexities.

Implementation Method 1

employing co-current or counter-current flow to circulate the feed stream

Methodology Applied
Scientific EffectCo-current flow:

Implementation Method 2

employing co-current or counter-current flow to circulate the feed stream

Methodology Applied
Scientific EffectCounter-current flow:

Implementation Method 3

circulate the feed stream through a closed-circuit flow path

Methodology Applied
Scientific EffectAdvection: Advection

Data Source

PatentEP4164780B1Plug flow reactor and method for providing a homogeneous feed stream within the plug flow reactor
Publication Date: 2025.10.01 BOEHRINGER INGELHEIM INT GMBH
  • EP4164780B1 patent drawingFigure 1
  • EP4164780B1 patent drawingFigure 2
  • EP4164780B1 patent drawingFigure 3

AI summary

A device and method for in-line homogenizing a non-uniform feed stream is described herein, which includes a plug flow reactor (PFR), a bypass line, and a pump in a closed-circuit flow path that allows for rapid homogenization of the non-uniform feed stream.