Microfluidic Cell Export via Staging Area and Pressure Differential

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Solution Overview

Problem

Current micro-fluidic devices lack an efficient method for selectively exporting specific groups of micro-objects, such as biological cells, from holding pens to external locations while maintaining their isolation and integrity.

Innovation Solution

The process involves selecting micro-objects using DEP forces, moving them to a staging area within the device, and then exporting them through a passage using a pressure differential generated by an export device, with options for self-closing or self-healing export interfaces to facilitate the transfer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cells are selected and moved within the micro-fluidic device using DEP forces, then the isolation and integrity of selected cells is maintained, but the complexity of the device increases due to the need for additional control mechanisms and export interfaces

Engineering Contradiction:
Improveisolation and integrity of selected cellsVSAvoiddevice complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The device is divided into distinct functional modules: holding pens for cell storage, a staging area for selected cells, and separate export interfaces. This segmentation allows independent control of each module, maintaining cell isolation while managing complexity through modular design. The holding pens contain individual cell groups, the staging area temporarily holds selected cells, and export interfaces provide controlled access points.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The staging area acts as an intermediary between the holding pens and the external environment. Selected cells are first moved to the staging area using DEP forces, then exported from there. This intermediate zone buffers the complexity of selection mechanisms from the export function, maintaining cell integrity while enabling controlled export.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If an export device is inserted through a self-closing or self-healing cover, then the isolation of cells during export is improved, but the ease of operation decreases due to the specialized interface requirements

Engineering Contradiction:
Improveisolation of cells during exportVSAvoidease of operation
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The export interface employs self-closing or self-healing covers that automatically restore their sealing function after export device insertion and removal. The system self-manages the isolation function without requiring manual intervention to maintain cell separation, thereby improving reliability while the automated nature reduces operational complexity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The self-healing cover utilizes a flexible membrane or thin film structure that can be temporarily penetrated by the export device and then automatically seals itself. This flexible structure maintains cell isolation during export while allowing straightforward device insertion and removal, balancing reliability and ease of operation.

Inventive Principle:
Principle #30Flexible shells and thin films

3Adaptability or versatility

If small volumes of cells are exported in various mediums, then the versatility of the micro-fluidic device is enhanced, but the manufacturing precision requirements increase to maintain isolation regions and export pathways

Engineering Contradiction:
Improveversatility in cell exportVSAvoidmanufacturing precision
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The micro-fluidic device is designed with universal holding pens, a common staging area, and multiple export interfaces that can handle various cell types and mediums. The same basic structure serves multiple functions: holding different cell groups, staging selected cells, and exporting through different interfaces. This multi-functionality enhances versatility while avoiding the need for separate precision-manufactured systems for each application.

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

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 precise and efficient export of selected micro-objects while maintaining isolation from other cells, ensuring their integrity and reducing contamination risks.

Implementation Method 1

directing a pattern of light into the micro-fluidic device such that the pattern of light surrounds the cells of the selected group and activates DEP forces that trap the cells of the selected group

Methodology Applied
Scientific EffectDEP forces (dielectrophoresis): Electrophoresis

Implementation Method 2

moving the selected group of cells to the staging area includes allowing gravity to attract the group of cells to the staging area

Methodology Applied
Scientific EffectGravity: Gravitation

Implementation Method 3

drawing the cells of the selected group through the passage in the enclosure includes generating a pressure differential that draws the cells of the group into the opening at the proximal end of the export device

Methodology Applied
Scientific EffectPressure differential: Pressure Gradient

Data Source

PatentEP3473699A1Exporting a selected group of micro-objects from a micro-fluidic device
Publication Date: 2019.04.24 BERKELEY LIGHTS INC
  • EP3473699A1 patent drawingFigure 1A~1B
  • EP3473699A1 patent drawingFigure 1C~1D
  • EP3473699A1 patent drawingFigure 2A~2B

AI summary

A group of micro-objects in a holding pen in a micro-fluidic device can be selected and moved to a staging area, from which the micro-objects can be exported from the micro-fluidic device. The micro-fluidic device can have a plurality of holding pens, and each holding pen can isolate micro-objects located in the holding pen from micro-objects located in the other holding pens or elsewhere in the micro-fluidic device. The selected group of micro-objects can comprise one or more biological cells, such as a clonal population of cells. Embodiments of the invention can thus select a particular group of clonal cells in a micro-fluidic device, move the clonal cells to a staging area, and export the clonal cells from the micro-fluidic device while maintaining the clonal nature of the exported group.