Cell Colony Selection via Transcription Factor Imaging

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Solution Overview

Problem

Current methods for selecting cell colonies or single cells with desired characteristics, such as those expressing specific proteins, are inefficient due to the heterogeneity of cell cultures and the destructive testing required to identify suitable clones, leading to the culturing of cells that do not possess the desired traits.

Innovation Solution

A method involving cultured cell colonies or single cells in a common continuous culture space where a ligand for the transcription factor is added, allowing for the assessment of transcription factor location changes using imaging systems, enabling the selection of cells with functional copies of the transcription factor without subdividing the culture space, and utilizing a robotic apparatus for automated selection and positioning.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If limiting dilution and multi-well plating are used to select cell colonies, then it is statistically unlikely that any well will contain more than one cell, but many wells have no cells and the process requires destructive testing of clones

Engineering Contradiction:
Improveselection accuracyVSAvoidselection efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies preliminary action by performing non-destructive assessment of cell colonies before making selection decisions. The method involves culturing cells to form colonies, then assessing them for desired characteristics prior to selection, allowing researchers to identify suitable clones in advance without destroying them during the assessment process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs self-service by using the cells' own biological properties for assessment. The method utilizes cell colony characteristics, growth patterns, or metabolic activities that naturally occur during culture to identify desired traits, eliminating the need for external destructive testing procedures.

Inventive Principle:
Principle #25Self-service

2Reliability

If clones are cultured and then destructively tested for desired characteristics, then the untested duplicates can be narrowed down to those exhibiting desired characteristics, but this process is inefficient because it entails culturing clones that turn out not to have the desired characteristic

Engineering Contradiction:
Improveselection reliabilityVSAvoidselection time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary assessment of cell colonies for desired characteristics before final selection. This allows researchers to identify suitable clones in advance based on observable traits during culture, eliminating the need to culture and then destructively test clones that would ultimately be rejected.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces destructive mechanical testing with non-destructive assessment methods. Instead of destroying clones to test for desired characteristics, the method uses observational techniques to evaluate colony properties during culture, substituting physical destruction with optical or metabolic monitoring.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Manufacturing precision

If cell colonies are subjected to destructive testing to identify desired characteristics, then suitable clones can be selected, but resource wastage occurs due to culturing cells that do not possess desired traits

Engineering Contradiction:
Improveclone selection precisionVSAvoidcell culture resource wastage
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The patent performs preliminary identification of clones with desired characteristics during the culture process itself. By assessing colonies for desired traits before selection decisions are made, the method prevents resource wastage by avoiding the culturing of clones that would ultimately be rejected, thereby improving resource utilization efficiency.

Inventive Principle:
Principle #10Preliminary action

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 method allows for the efficient and non-destructive selection of cell colonies or single cells with desired characteristics, reducing resource wastage and improving the efficiency of identifying cells with functional proteins by assessing changes in transcription factor location through imaging, facilitating the selection of cells with specific traits.

Implementation Method 1

assessment of transcription factor location changes using imaging systems

Methodology Applied
Scientific EffectOptical detection: Light

Data Source

PatentEP2682187B1Selection method and apparatus
Publication Date: 2017.09.13 MOLECULAR DEVICES LLC
  • EP2682187B1 patent drawingFigure 1
  • EP2682187B1 patent drawingFigure 2
  • EP2682187B1 patent drawingFigure 3A~3B

AI summary

A method and an apparatus for selecting a cultured cell colony or a cultured single cell having a desired characteristic are disclosed. The method includes providing a plurality of cultured cell colonies or cultured single cells in a common culture space. The cell colonies or single cells are heterogeneous in respect of the desired characteristic. A treatment is applied to the cell colonies or to the single cells, while the cell colonies or the single cells are in the common culture space. The treatment elicits a change in a function of a cellular component of those cell colonies or single cells which have the desired characteristic. Individual ones of the cell colonies or of the single cells are then assessed, in the common culture space, for a marker of the change in the function. The method also comprises selecting at least one but not all of the cell colonies or of the single cells. The selection takes account of the assessment for the marker to determine expected possession of the desired characteristic. Each selected cell colony or single cell is expected to have the desired characteristic on the basis of the assessment. The method also includes providing an indication of the spatial position of at least one of the cell colonies or of the single cells that are selected.