Cell Sorter with Fluorescence Imaging and Hydraulic Extraction

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Solution Overview

Problem

Current cell sorting technologies face challenges in accurately and efficiently extracting specific cells from a culture plate based on fluorescence imaging, often requiring harsh removal processes and risking damage to the needle due to inadequate positioning and adherence issues.

Innovation Solution

A cell sorter system that includes a fluorescence imager, a cell extraction module with a needle and motorized translation stages for precise positioning, and a sensor to prevent needle contact with the plate, allowing hydraulic removal of selected cells while minimizing damage and using a de-adhering agent to reduce cell adherence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a needle is used to extract cells from a cell culture plate, then cell extraction can be performed, but the needle may come into contact with the plate bottom causing damage

Engineering Contradiction:
Improvecell extraction capabilityVSAvoidneedle damage risk
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system performs fluorescence imaging and cell selection before extraction, and uses a sensor to detect needle proximity to the plate bottom before contact occurs. This preliminary detection and positioning prevents needle damage while maintaining extraction capability

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

A sensor provides real-time feedback on needle position relative to the plate bottom, allowing the system to adjust needle depth dynamically. This feedback mechanism prevents the needle from contacting the plate bottom while enabling effective cell extraction

Inventive Principle:
Principle #23Feedback

2Measurement precision

If cells are firmly adhered to the cell culture plate, then cell positioning is stable for imaging, but cell extraction requires harsh removal processes

Engineering Contradiction:
Improvecell positioning stabilityVSAvoidharsh removal process damage
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system changes the chemical parameter of the extraction environment by applying a de-adhering agent to the needle or plate surface. This parameter change reduces adhesion strength temporarily during extraction while maintaining stable cell positioning during imaging

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

A de-adhering agent acts as an intermediary substance between the cell and plate surface during extraction. This intermediary reduces the harmful adhesion force that would otherwise require harsh mechanical removal processes

Inventive Principle:
Principle #24Intermediary (Mediator)

3Manufacturing precision

If the needle is positioned precisely to extract a specific cell, then selective extraction is achieved, but positioning accuracy may be compromised by adherence variations

Engineering Contradiction:
Improvecell selection accuracyVSAvoidneedle positioning accuracy
Core Design Contradiction:
Manufacturing precisionVSMeasurement precision

Solution Approach 1:

The system replaces mechanical positioning alone with a combination of optical guidance (fluorescence imaging) and sensor-based feedback control. This substitution maintains positioning accuracy despite variations in cell adherence to the plate

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

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 precise and gentle extraction of cells based on fluorescence imaging, reducing the risk of needle damage and allowing for accurate, selective removal without harsh processes, facilitating efficient cell sorting and potential applications in drug discovery and biosensor processes.

Implementation Method 1

a fluorescence imager configured to view the cell culture plate, through bottom of the cell culture plate, to capture one or more fluorescence images of the fluorescently labeled sample of cells

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

a needle configured to hydraulically remove the first cell from the cell culture plate

Methodology Applied
Scientific EffectHydraulic removal: Hydraulic Press

Data Source

PatentUS11873475B2Systems and methods for cell sorting and cell extraction
Publication Date: 2024.01.16 BIOLOOMICS INC
  • US11873475B2 patent drawing
  • US11873475B2 patent drawing
  • US11873475B2 patent drawing

AI summary

A cell sorter includes a base for holding a cell culture plate containing a fluorescently labeled sample of cells, a fluorescence imager for viewing the cell culture plate, through bottom of the cell culture plate, to capture one or more fluorescence images of the fluorescently labeled sample of cells, and a cell extraction module for extracting a cell selected based on the one or more fluorescence images. The cell extraction module includes a needle for hydraulically removing the selected cell from the cell culture plate, and a motorized translation stage for translating the needle in a z-dimension to reach the selected cell from above. The cell sorter further includes a motorized translation stage for translating one of the needle and the cell culture plate in x- and y-dimensions, relative to the other one of the needle and the cell culture plate, to position the needle over selected first cell.