Micro-well Array Device for High-Throughput Cell Capture

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Solution Overview

Problem

High-throughput microfluidic systems face challenges in accurately capturing and isolating individual cells and cell clusters from fluid samples, particularly in capturing rare cells and maintaining cell viability, due to limitations in geometric arrangements and access to captured cells.

Innovation Solution

A micro-well array device with varying micro-well sizes and a magnet component that applies a flow-independent variable magnetic force to capture and hold target entities, allowing for the isolation of individual cells and clusters without the need for a wash step, enabling efficient capture and analysis of cells from fluid samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple cells are combined and lysed to increase throughput, then processing speed is improved, but cell-to-cell variation information is lost

Engineering Contradiction:
Improveprocessing speedVSAvoidcell-to-cell variation information
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The system segments the processing by providing individual access to each captured cell through removable micro-well plates. Each cell can be individually manipulated, lysed, and analyzed while maintaining spatial correspondence with its capture location, thus preserving cell-to-cell variation information while enabling high-throughput processing through parallel operations.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If a magnet component applies magnetic force to capture cells, then capture accuracy is improved, but cell viability may be compromised

Engineering Contradiction:
Improvecapture accuracyVSAvoidcell viability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The magnet component is designed to be movable relative to the micro-well plate, allowing dynamic control of magnetic force application. The magnet can be positioned close to the plate for high-accuracy capture, then moved away to reduce magnetic force on captured cells, thereby maintaining cell viability while achieving accurate capture when needed.

Inventive Principle:
Principle #15Dynamics

3Manufacturing precision

If micro-wells are designed with fixed geometric arrangements to capture individual cells, then isolation accuracy is improved, but the ability to capture both individual cells and cell clusters is reduced

Engineering Contradiction:
Improveisolation accuracyVSAvoidcapture capability for different cell types
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The micro-well plate provides precise geometric arrangements for capturing individual cells. Additionally, larger chambers or wells are incorporated to accommodate cell clusters that do not fit in standard micro-wells, allowing the system to handle both individual cells and clusters within the same platform while maintaining high isolation accuracy for each type.

Inventive Principle:
Principle #16Partial or excessive action

4Reliability

If the micro-well plate is sealed to maintain cell viability, then cell health is improved, but access to captured cells for manipulation is reduced

Engineering Contradiction:
Improvecell healthVSAvoidaccess to captured cells
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The micro-well plate is designed with a removable lid or seal that can be dynamically opened and closed. The plate remains sealed during storage and transport to maintain cell health, but can be quickly opened when manipulation or analysis is required, providing both cell viability protection and easy access when needed.

Inventive Principle:
Principle #15Dynamics

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

The system effectively captures and isolates individual cells and clusters with high accuracy and consistency, retaining cell-to-cell variations for analysis, improving studies of diseases like cancer by maintaining cell viability and reducing the risk of losing target cells.

Implementation Method 1

a magnet component that applies a flow-independent variable magnetic force to capture and hold target entities

Methodology Applied
Scientific EffectMagnetic force: Magnetism

Data Source

PatentUS11173488B2High-throughput particle capture and analysis
Publication Date: 2021.11.16 PURDUE RES FOUND
  • US11173488B2 patent drawing
  • US11173488B2 patent drawing
  • US11173488B2 patent drawing

AI summary

Microfluidic systems and methods are described for capturing magnetic target entities bound to one or more magnetic beads. The systems include a well array device that includes a substrate with a surface that has a plurality of wells arranged in one or more arrays on the surface. A first array of wells is arranged adjacent to a first location on the surface. A second and subsequent arrays, if present, are arranged sequentially on the surface at second and subsequent locations. When a liquid sample is added onto the substrate and caused to flow, the liquid sample will flow across the first array first and then flow across the second and subsequent arrays in sequential order. The wells in the first array each have a size that permits entry of only one target entity into the well and each well in the first array has approximately the same size.