Microparticle Co-Culture System for High-Throughput Strain Selection
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Solution Overview
Problem
Current methods are inadequate for high-throughput isolation and testing of beneficial microbial strains due to limitations in culturing and interacting microbial and eukaryotic cells, particularly in mimicking physiological conditions such as anaerobic environments, which restricts the ability to study large numbers of bacterial strains and their interactions effectively.
Innovation Solution
A microparticle system with two cultivation spaces allows for the co-culture of microbial and eukaryotic cells, enabling molecular exchange and phenotypic sorting, thereby facilitating the identification of beneficial strains and their effects, including probiotic effects, through compound diffusion and FACS analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If droplet-based microfluidics is used to encapsulate cells, then throughput is improved, but physiological interaction between cells is lost
Solution Approach 1:
The invention segments the cultivation environment into distinct spatial zones (first cultivation space for bacterial cells, second cultivation space for eukaryotic cells) within a unified microparticle structure, allowing high-throughput processing while maintaining physiological interaction through controlled molecular exchange between segments
Solution Approach 2:
The microparticle wall acts as an intermediary structure that permits molecular exchange (nutrients, waste products, signaling molecules) between the bacterial and eukaryotic cultivation spaces while maintaining physical separation, thus enabling physiological interaction without compromising the high-throughput encapsulation benefit
2Productivity
If multiple microtiter plates are used for parallel testing, then throughput is improved, but device complexity increases
Solution Approach 1:
The invention merges the functions of multiple microtiter plates into a single microparticle-based system, integrating high-throughput encapsulation, co-cultivation, and phenotypic sorting capabilities in one unified device, thereby improving throughput while reducing overall device complexity
Solution Approach 2:
The microparticle system serves multiple functions simultaneously: it acts as a cultivation chamber, a sorting unit, and an interaction platform, eliminating the need for separate microtiter plates and reducing device complexity while maintaining high throughput
3Productivity
If mammalian and bacterial cells are co-located in a droplet, then throughput is improved, but selection conditions are compromised
Solution Approach 1:
The invention applies local quality by creating distinct cultivation environments within the microparticle - an anaerobic first cultivation space for bacterial cells and an aerobic second cultivation space for eukaryotic cells - allowing each cell type to receive appropriate selection conditions while maintaining high throughput
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 approach enables the unprecedented ultrahigh-throughput selection and isolation of up to 10^9 microbial strains, overcoming previous limitations by allowing physiological interaction and selection conditions, such as anaerobic growth, thus identifying beneficial microbial strains effectively.
Implementation Method 1
the wall surrounding the core allows for the exchange of molecules as, salts, nutrients, peptides, chemicals and other compounds in order for the cells in the first cultivation space to interact with the cells in the second cultivation space and vice versa
Data Source
AI summary
Cultivation and/or test-system comprising at least two cultivation spaces combined in a microparticle, wherein the sperically shaped microparticle comprises, (i) a first cultivation space in the center core of said spherically shaped microparticle, (ii) a second cultivation space in the wall surrounding the core of said microparticle, (iii) wherein the wall surrounding the core allows for the exchange of molecules as, salts, nutrients, peptides, chemicals and other compounds in order for the cells in the first cultivation space to interact with the cells in second cultivation space and vice versa. In the test system, the cells are co-cultivated and the microparticles are then selected based on the phenotype of the cells in the first or second cultivation space.