Automated Organ Decellularization Bioreactor With Pressure Feedback

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Solution Overview

Problem

The limited availability of donor organs for lung transplantation and the challenges of immunosuppression and chronic rejection in clinical lung transplantation are addressed by developing an automated bioreactor system for decellularizing organs, which reduces human intervention and enhances sterility, consistency, and efficiency in the decellularization process.

Innovation Solution

An automated bioreactor system with a main chamber, reagent and perfusion conduits, pumps, and a control system that automates the decellularization process, minimizing human interaction and ensuring sterility and consistency by controlling reagent flow and waste decontamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual decellularization protocols are used, then human flexibility in handling complex organ structures is maintained, but contamination risk increases and consistency decreases

Engineering Contradiction:
Improveconsistency of decellularizationVSAvoidmanual intervention level
Core Design Contradiction:
ReliabilityVSExtent of automation

Solution Approach 1:

The system enables self-service automation where the bioreactor automatically executes decellularization protocols without requiring continuous manual intervention. The automated control system manages reagent delivery, perfusion pressure, and flow rates, allowing the system to perform complex decellularization tasks independently while maintaining consistent results across different organs and operators.

Inventive Principle:
Principle #25Self-service

2Reliability

If automated bioreactor system is implemented, then sterility and consistency are enhanced, but system complexity increases

Engineering Contradiction:
Improvesterility assuranceVSAvoidsystem component count
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The bioreactor system is divided into distinct functional modules including a perfusion system for delivering reagents, a control system for managing parameters, and a waste decontamination system for handling contaminated fluids. This segmentation allows each component to perform its specific function independently, making the overall complex system more manageable and easier to maintain sterility through dedicated pathways for each function.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The control system acts as an intermediary between the operator and the complex bioreactor components. It receives protocol parameters from the operator and automatically translates them into precise control signals for pumps, valves, and sensors, thereby simplifying the operator's interaction with the complex system while maintaining high sterility standards through automated execution.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If manual decellularization is performed, then process adaptability to individual organ variations is maintained, but time consumption and resource waste increase

Engineering Contradiction:
Improvedecellularization throughputVSAvoidoperational simplicity
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The system automatically adjusts critical process parameters including perfusion pressure, flow rate, and reagent concentration based on pre-programmed protocols. The control system monitors these parameters in real-time and makes precise adjustments to optimize decellularization for each organ type, eliminating the need for manual adaptation while maintaining high productivity through standardized, repeatable parameter sequences that can be quickly adjusted for different organs.

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

The system increases the likelihood of obtaining a viable and structurally sound decellularized organ by reducing contamination risks and enhancing the efficiency and consistency of the decellularization process, thereby improving the potential for successful tissue engineering and transplantation.

Implementation Method 1

At least one perfusion pump is configured to drive the flow of the liquid phase reagent through the at least one perfusion conduit

Methodology Applied
Scientific EffectPump: Pump

Implementation Method 2

At least one perfusion pressure sensor detects a pressure of the liquid phase reagent flowing through the at least one perfusion conduit

Methodology Applied
Scientific EffectPressure detection:

Implementation Method 3

A control system receives an input representative of a desired pressure of the liquid phase reagent flowing through the at least one perfusion conduit, receives an input of the pressure detected by the at least one perfusion pressure sensor, and outputs a signal to control the at least one perfusion pump

Methodology Applied
Scientific EffectFeedback control: Feedback

Implementation Method 4

At least one reagent conduit configured to deliver the liquid phase reagent from the at least one reagent chamber to the main chamber through the at least one reagent inlet

Methodology Applied
Scientific EffectFluid transport:

Implementation Method 5

At least one perfusion conduit is configured to deliver the liquid phase reagent from the at least one reagent outlet into the organ through the at least one perfusion inlet

Methodology Applied
Scientific EffectPerfusion:

Data Source

PatentUS12458015B2Automated bioreactor system, system for automatically implementing protocol for decellularizing organ, and waste decontamination system
Publication Date: 2025.11.04 UNITED THERAPEUTICS CORP
  • US12458015B2 patent drawing
  • US12458015B2 patent drawing
  • US12458015B2 patent drawing

AI summary

An automated bioreactor system for decellularizing an organ includes a main chamber for containing the organ. The system further includes a reagent chamber containing a liquid phase reagent. A reagent conduit delivers the liquid phase reagent to the main chamber, and a perfusion conduit delivers the reagent from the reagent outlet in the main chamber into the organ. A perfusion pump drives the flow of the reagent. A perfusion pressure sensor detects a pressure of the flowing reagent. A control system controls the perfusion pump to drive the flow of the reagent based on a received input representative of a desired pressure and a received input of the detected pressure. The control system may automatically perform all of the steps of a decellularization protocol based on sensor input. An automated waste decontamination system may also be provided.