Cell Colony Picking System Using Imaging for Monoclonality

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Solution Overview

Problem

Current automated systems for screening and selecting cell colonies are inefficient in identifying and picking monoclonal colonies, requiring multiple steps, large quantities of reagents, and resulting in low cell viability.

Innovation Solution

A method and apparatus for growing and identifying monoclonal colonies by plating cells at low density, capturing initial and follow-up images to determine monoclonality, and using a picking head to transfer viable colonies to a target environment, reducing the need for extensive reagents and improving viability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If single cells are isolated using FACS and plated in high-density multiwell plates, then monoclonal colonies can be produced, but large quantities of reagents and large numbers of multiwell plates are required and cell viability is low

Engineering Contradiction:
Improvemonoclonal colony productionVSAvoidreagent consumption
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The system divides the colony picking process into distinct functional modules: imaging system for colony detection, analysis system for monoclonality determination, and picking head for physical transfer. This segmentation allows each component to be optimized independently, reducing overall resource consumption while maintaining reliability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses digital imaging to create a virtual map of colony locations and characteristics before physical picking. This optical copying approach eliminates the need for manual inspection and enables automated decision-making, reducing reagent waste through precise targeting.

Inventive Principle:
Principle #26Copying

2Reliability

If single cells are isolated using FACS and plated in high-density multiwell plates, then monoclonal colonies can be produced, but large numbers of multiwell plates are required and cell viability is low

Engineering Contradiction:
Improvemonoclonal colony productionVSAvoidmultiwell plate consumption
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The system combines multiple functions into a single automated platform: cell plating, incubation monitoring, colony imaging, data analysis, and physical picking all occur in one integrated system. This merging eliminates the need for multiple separate multiwell plates and manual transfer steps, reducing consumable usage while maintaining colony viability.

Inventive Principle:
Principle #5Merging (Combining)

3Productivity

If current automated systems are used for screening and selecting cell colonies, then colony selection can be performed, but the systems are ill-suited for identifying and picking monoclonal colonies

Engineering Contradiction:
Improvecolony selection capabilityVSAvoidmonoclonality identification accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system implements a feedback loop where colonies are imaged, analyzed for monoclonality characteristics, and then picked based on the analysis results. The picking head receives real-time guidance from the analysis system, ensuring that only colonies meeting monoclonality criteria are selected, thereby improving both productivity and precision.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system replaces manual colony inspection and selection with automated optical imaging and computer-based analysis. This substitution enables precise identification of monoclonal colonies based on quantitative image features rather than subjective manual assessment, improving both throughput and accuracy.

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

4Reliability

If multiple steps and instruments are used to produce monoclonal colonies, then monoclonal colonies can be obtained, but the process is complex and cell viability is low

Engineering Contradiction:
Improvemonoclonal colony productionVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The automated system performs multiple functions using a single integrated platform: it plates cells, monitors growth, images colonies, analyzes monoclonality, and picks selected colonies. This multi-functionality eliminates the need for multiple separate instruments and manual操作步骤, reducing process complexity while maintaining production reliability.

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

Data Source

PatentUS12173270B2Cell colony picking system
Publication Date: 2024.12.24 MOLECULAR DEVICES LLC
  • US12173270B2 patent drawing
  • US12173270B2 patent drawing
  • US12173270B2 patent drawing

AI summary

Systems, including methods and apparatus, for growing viable monoclonal colonies, identifying them as monoclonal after their viability has been demonstrated, and picking and placing them into a target environment. The methods may include plating cells at low density in a well, capturing at a first time shortly after plating a series of vertically spaced-apart images of the well showing locations of the cells, capturing at a second, later time images of the same well showing locations of candidate cell colonies, determining a likelihood that the candidate colonies are monoclonal based on information in the first set of images, and, based on the likelihood, picking candidate colonies using a picking head for transfer to a target environment.