Cell Culture Phaseguide Sub-Volumes for In Vivo Replication

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Solution Overview

Problem

Current laboratory apparatuses fail to accurately replicate in vivo conditions for cultivating life-based organic particles, such as cells and tissues, leading to experimental flaws and difficulties in nutrient and waste management, and are inadequate for large-scale simultaneous testing.

Innovation Solution

A hollow volume divided by phaseguides into sub-volumes with connected fluid conduits allows for the creation of realistic cultivation environments, enabling controlled transport of nutrients and waste, and supporting life-based particles in a gel-like substance, mimicking in vivo conditions for large-scale assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cultivation chambers are used, then device simplicity is maintained, but in vivo condition replication accuracy deteriorates

Engineering Contradiction:
Improvein vivo condition replication accuracyVSAvoidapparatus structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The cultivation chamber is divided into multiple sub-volumes (first sub-volume with cells, second sub-volume without cells) separated by phaseguides. This segmentation allows different regions to replicate different aspects of in vivo conditions independently, improving overall physiological accuracy while managing complexity through modular design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Phaseguides are introduced as intermediary structures between sub-volumes to control fluid menisci and enable selective substance transport. These intermediaries facilitate controlled nutrient supply and waste removal while maintaining distinct microenvironments, thereby improving condition replication without requiring direct contact between all components.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional single-volume chambers are used, then device complexity is reduced, but nutrient and waste management capability deteriorates

Engineering Contradiction:
Improvelarge-scale simultaneous testing capacityVSAvoidconduit and phaseguide system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The chamber is segmented into multiple sub-volumes that can be independently filled and controlled through separate fluid conduits. This allows parallel processing of multiple cell samples simultaneously, dramatically increasing productivity while the modular conduit system manages fluid distribution efficiently across all sub-volumes.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The phaseguide structures serve multiple functions: they define menisci, control fluid flow directions, enable selective substance transport between sub-volumes, and maintain structural integrity. This multi-functionality reduces the need for additional separate components, managing complexity while supporting large-scale testing capabilities.

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

3Reliability

If flat chamber surfaces are used, then manufacturing simplicity is maintained, but cell cultivation accuracy deteriorates

Engineering Contradiction:
Improvecell cultivation physiological accuracyVSAvoidchamber surface fabrication difficulty
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The phaseguides are designed with curved surfaces rather than flat surfaces, creating spherical or meniscus-shaped liquid interfaces. This curvature better replicates the natural curved surfaces cells encounter in vivo, improving cultivation accuracy. The curved geometry can be achieved through standard molding techniques, maintaining reasonable ease of manufacture.

Inventive Principle:
Principle #14Spheroidality (Curvature)

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

This setup enhances the viability of cells and tissues by accurately replicating in vivo conditions, facilitating large-scale, controlled experiments with improved nutrient and waste management, and allows for precise manipulation of substances across sub-volumes.

Implementation Method 1

A phaseguide may be defined as a structure, in a volume that is to be filled with or emptied of a liquid, that limits the ability of the meniscus of a body of liquid to advance or recede in the volume, thereby defining an interface between the liquid and another substance

Methodology Applied
Scientific EffectMeniscus pinning: Surface Tension

Implementation Method 2

Advancement over such a sharp edge requires a change of the principal radii of a fluid-fluid meniscus, leading to a higher pressure drop over the meniscus thus representing a pressure barrier

Methodology Applied
Scientific EffectPressure drop: Pressure Gradient

Data Source

PatentUS10900008B2Apparatuses for and methods of processing cells and related structures
Publication Date: 2021.01.26 LEIDEN UNIVERSITY
  • US10900008B2 patent drawing
  • US10900008B2 patent drawing
  • US10900008B2 patent drawing

AI summary

Apparatus for processing life-based organic particles, including particles selected from the list comprising cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos, comprises a hollow volume (10) that (a) is internally divided into at least first (14), second (16) and third (17) sub-volumes by at least two phaseguides (12, 13) formed inside the volume and (b) includes parts that are relatively upstream and relatively downstream when judged with reference to the movement of a meniscus or a bulk liquid in the volume (10). The apparatus includes at least first, second and third fluid conduits (19, 21, 22) connected to permit fluid communication between the upstream exterior of the volume (10) and a respective said sub-volume (14, 16, 17); and at least one further conduit (24) connected to permit fluid communication between the downstream exterior of the volume (10) and a said sub-volume. The first sub-volume (14) contains one or more life-based particles supported in or by a gel or gel-like substance; and the second sub-volume (16) communicates with the first sub-volume so as to permit transport of substances between the first and second sub-volumes (14, 16) and contains at least one gel or gel-like substance.