Bioreactor Addition Tube Check Valve for Controlled Reagent Delivery

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing bioreactor systems face challenges in controlling the addition of reagents, leading to unpredictable delivery and potential cell death due to toxic conditions when the delivery orifice is immersed, and inefficient distribution when suspended above the medium.

Innovation Solution

A bioreactor design incorporating a check valve in proximity to the delivery orifice of the addition tube, which allows fluid flow only in one direction, preventing backflow and ensuring controlled reagent delivery directly into the cell culture medium, with adjustable orifice positioning and suitable check valve constructions to minimize stagnant zones and pressure fluctuations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If the delivery orifice is immersed in the cell culture medium, then the reagent can be delivered directly into the medium, but cells may enter the tube and be subjected to highly toxic conditions leading to cell death

Engineering Contradiction:
Improvereagent delivery controlVSAvoidcell exposure to toxic conditions
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

A check valve is introduced as an intermediary component between the addition tube and the bioreactor vessel. This check valve allows reagent to flow from the addition tube into the vessel while preventing backflow that would expose cells to toxic reagent concentrations. The check valve thus mediates the interaction between the reagent delivery system and the cell culture environment, enabling direct medium immersion for efficient distribution while protecting cells from harmful effects.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If the delivery orifice is suspended above the medium, then cells are protected from toxic conditions, but the reagent may go primarily into the foam layer on top of the medium, preventing proper distribution

Engineering Contradiction:
Improvecell exposure to toxic conditionsVSAvoidreagent distribution efficiency
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The check valve serves as a mediator that enables the delivery orifice to be positioned within the medium for efficient distribution while preventing the harmful backflow effect. By allowing forward flow into the vessel and blocking reverse flow, the check valve decouples the distribution efficiency benefit of immersion from the harmful cell exposure effect, enabling optimal positioning without compromising cell safety.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Device complexity

If the pump is run intermittently with fixed addition program, then the system is simple to operate, but reagent may be delivered by dripping or diffusion even when the pump is stopped, causing poor control of the reagent supply

Engineering Contradiction:
Improvepump control systemVSAvoidreagent supply control precision
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The check valve provides passive feedback control by automatically responding to pressure differential changes. When pump pressure exceeds backpressure, the valve opens to allow reagent flow; when pump pressure drops below backpressure, the valve closes to prevent backflow and uncontrolled delivery. This feedback mechanism eliminates the need for complex active control systems while ensuring precise reagent supply control, as the valve state automatically reflects the pressure balance between delivery and backpressure forces.

Inventive Principle:
Principle #23Feedback

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

Ensures precise and even distribution of reagents, preventing local high concentrations and cell exposure to toxic conditions, while maintaining efficient fluid delivery and distribution within the bioreactor.

Implementation Method 1

a check valve (7;27) is arranged in proximity of, or adjacent, the delivery orifice such that it allows flow of a fluid in the direction from the addition tube into the inner volume (3;23) and blocking flow in the reverse direction

Methodology Applied
Scientific EffectCheck valve mechanism: Valve

Implementation Method 2

the reagents are evenly distributed

Methodology Applied
Scientific EffectConvection: Convection

Implementation Method 3

reagent may be delivered by dripping or diffusion

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3039115B2Bioreactor with addition tube
Publication Date: 2022.04.06 CYTIVA SWEDEN AB
  • EP3039115B2 patent drawingFigure 1
  • EP3039115B2 patent drawingFigure 2
  • EP3039115B2 patent drawingFigure 3

AI summary

The invention discloses a bioreactor with a vessel defining an inner volume, agitation means and at least one addition tube, wherein a delivery orifice in the addition tube is located within the inner volume and a check valve is arranged in proximity of the delivery orifice for allowing flow of a fluid in the direction from the addition tube into the inner volume of the vessel and blocking flow in the reverse direction.