MicroATF Perfusion Filter for Small-Volume Bioprocessing

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Solution Overview

Problem

Conventional filtration systems are ill-suited for small-scale biotechnology applications, requiring high volumes and materials, making them costly and complex for processing small volumes of cell culture media, and centrifuges cannot validate commercial filtration processes effectively.

Innovation Solution

A micro alternating tangential flow (microATF) perfusion filter system comprising a hollow cylinder with a permeate and retentate chamber, connected via a filter element, allowing for efficient filtration and perfusion of cell culture media in volumes as low as 15 mL or less, using a source of alternating pressure to facilitate fluid communication.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional filtration systems are used for small-scale biotechnology applications, then filtration can be performed, but the systems require high volumes and materials, making them costly and complex

Engineering Contradiction:
Improvevolume of cell culture mediaVSAvoidcomplexity of filtration system
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent creates a microscale copy of conventional filtration systems, replicating the essential filtration functionality in a miniaturized format. The micro filtration device copies the chamber structure and filter element arrangement of larger systems but scales it down to handle volumes of 15 mL or less, reducing material requirements and system complexity while maintaining filtration effectiveness

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent changes the physical parameters of the filtration system by scaling down dimensions to microscale. The device is specifically designed to operate with small volumes (15 mL or less) by adjusting chamber sizes, filter surface areas, and flow path dimensions, thereby resolving the contradiction between handling small volumes and maintaining effective filtration capability

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If conventional filtration systems are used for small volumes, then filtration can be performed, but the systems require high volumes and materials, increasing costs

Engineering Contradiction:
Improvevolume of cell culture mediaVSAvoidmaterials required
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The micro filtration device creates a scaled-down copy of conventional systems that uses proportionally less material. By replicating the essential filtration chambers and filter elements in microscale, the device reduces material consumption while maintaining filtration functionality for small volumes

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The filtration system is segmented into discrete microcomponents including a micro retentate chamber, micro permeate chamber, and integrated filter element. This segmentation allows each component to be optimized for minimal material usage while performing its specific function efficiently in small-volume applications

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If centrifuges are used to process small volumes, then processing can be performed, but centrifuges cannot validate commercial filtration processes effectively

Engineering Contradiction:
Improveability to process small volumesVSAvoidvalidation of commercial filtration processes
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The micro filtration device copies the actual filtration process used in commercial applications, allowing it to serve as a valid validation model. Unlike centrifuges which use a different separation mechanism, the micro filtration device replicates the membrane filtration process, enabling results to be directly extrapolated to commercial-scale filtration operations

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The device serves multiple functions: it can process small volumes like centrifuges, but also validates commercial filtration processes like full-scale systems. The micro filtration device acts as a universal platform that bridges the gap between small-volume processing needs and commercial process validation requirements

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

4Quantity of substance

If conventional bioprocessing vessels are used, then filtration can be performed, but the vessels have a lower volume limit of approximately 1 L, necessitating high quantities of materials and personnel

Engineering Contradiction:
Improvevolume of cell culture mediaVSAvoidmaterials and personnel required
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent fundamentally changes the volume parameter from liters to milliliters (15 mL or less). By redesigning the filtration system with microscale chambers and components, the device can effectively process volumes that are 60-67 times smaller than conventional vessels, thereby reducing material and personnel requirements proportionally

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

Enables efficient filtration and perfusion of small volumes of cell culture media, reducing costs and maintaining data comparability to larger scale processes, without the need for centrifugation, thus addressing the limitations of conventional systems.

Implementation Method 1

withdrawing cells in cell culture media through a lumen of one or more hollow fiber filters

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

an inlet positioned over the retentate chamber for communication with a source of alternating positive or negative pressure

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Data Source

PatentUS11946033B2Micro alternating tangential flow perfusion filter, micro bioreactor, and methods of use thereof
Publication Date: 2024.04.02 REPLIGEN CORP
  • US11946033B2 patent drawing
  • US11946033B2 patent drawing
  • US11946033B2 patent drawing

AI summary

A micro alternating tangential flow (microATF) perfusion filter includes a hollow cylinder having a proximal end and a distal end. The proximal end is connected in series to a permeate chamber, followed by a retentate chamber. The proximal end either (i) terminates in or at the permeate chamber, or (ii) terminates in or at the retentate chamber. The portion of the proximal end within the permeate chamber, in a case of (ii), possesses at least one opening allowing fluid communication between an inside of the hollow cylinder and the permeate chamber. The microATF perfusion filter further includes an inlet, positioned over the retentate chamber, for communication with a source of positive or negative pressure, and an outlet, positioned in a wall of the permeate chamber, which can be connected to a check valve, which, in turn, can be connected to a hydrophobic fluid vent filter.