Parallel Bioreactor with Integrated Fluid Injection and Gas Switching

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Solution Overview

Problem

Current bioreactor systems face challenges in efficiently controlling environmental parameters like pH and dissolved oxygen at small scales, leading to suboptimal conditions for microbial growth and strain selection, particularly in transitioning from microtiter plates and shake flasks to industrial-scale bioprocesses.

Innovation Solution

A parallel integrated bioreactor system with integrated fluid injection and mixing devices, constructed using a simple molding process, enables precise control of pH and dissolved oxygen levels through fluid injection and gas switching, allowing for high cell density growth and scalable experimentation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If bench-scale bioreactors are used to improve control over environmental variables and oxygenation, then the ability to achieve higher cell densities is improved, but the cost and time required to test multiple combinations of strains and environmental conditions increases

Engineering Contradiction:
Improvecontrol over environmental variablesVSAvoidthroughput of experiments
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The system divides the bioreactor functionality into multiple parallel micro-reactors (e.g., 96-well plate format), allowing simultaneous experimentation with multiple strain-condition combinations. Each well functions as an independent mini-bioreactor with individual environmental control, enabling high-throughput screening while maintaining controlled conditions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates scaled-down copies of bench-scale bioreactor functionality in micro-scale platforms. These micro-bioreactors replicate the controlled environment, oxygenation, and monitoring capabilities of larger reactors but at a fraction of the cost and complexity, allowing parallel testing of multiple conditions.

Inventive Principle:
Principle #26Copying

2Productivity

If microtiter plates are used for high-throughput screening, then the number of experiments that can be performed in parallel is improved, but the oxygen transfer capacity and control over environmental parameters deteriorates

Engineering Contradiction:
Improvenumber of parallel experimentsVSAvoidoxygen transfer capacity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system incorporates pneumatic sparging (gas sparging through porous materials) and hydraulic circulation systems within the micro-bioreactors to dramatically improve oxygen transfer rates. These fluid dynamics-based oxygenation methods enable high cell densities while maintaining the high-throughput parallel experimentation capability.

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Ease of operation

If shake flasks are used for strain screening, then the simplicity and ease of operation is improved, but the ability to achieve high oxygen concentrations and controlled conditions deteriorates

Engineering Contradiction:
Improvesimplicity of operationVSAvoidcontrol over environmental parameters
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The micro-bioreactor platform integrates multiple functions into a single system: environmental control (temperature, pH, oxygen), monitoring (optical sensors for cell density, gas exchange), and high-throughput parallel operation. This multi-functional design maintains ease of operation while providing rigorous environmental control comparable to bench-scale reactors.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 system provides improved oxygen transfer rates and controlled environmental conditions, enabling the identification of optimal strains and conditions for industrial-scale bioprocesses by allowing multiple experiments to be performed in parallel with reduced costs and increased precision.

Implementation Method 1

The PIB device further comprises a peristaltic oxygenating mixer, which mixes the growth chamber

Methodology Applied
Scientific EffectPeristalsis: Peristalsis

Implementation Method 2

The dissolved oxygen in the PIB device may be controlled by changing the oxygen concentration in the actuation gas

Methodology Applied
Scientific EffectGas exchange:

Implementation Method 3

at least one metered fluid injector to pass metered amounts of fluid from the reservoir into the growth chamber

Methodology Applied
Scientific EffectFluid injection: Injector

Implementation Method 4

at least one sensor located within the growth chamber, wherein the sensor measures the pH properties of the growth chamber

Methodology Applied
Scientific EffectpH sensing:

Data Source

PatentUS9248421B2Parallel integrated bioreactor device and method
Publication Date: 2016.02.02 MASSACHUSETTS INST OF TECH
  • US9248421B2 patent drawing
  • US9248421B2 patent drawing
  • US9248421B2 patent drawing

AI summary

In one embodiment, the present invention introduces integrated fluid injection and mixing devices to enable pH control in a miniature parallel integrated bioreactor array system. In another embodiment, the environmental conditions of the growth chamber is enabled through fluidic injections in a miniature parallel cell culture system. In still another embodiment, the present invention utilizes gas switches to control oxygen concentration within a miniature parallel integrated bioreactor array.