Microfluidic Cell Capture System with Magnetic Separation

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Solution Overview

Problem

Current cell capture systems in cellular analysis are limited by their inability to perform multiple analyses on the same cell, allow arbitrary cell subpopulation sorting, and maintain cell viability during capture and retrieval, while also being prone to clogging and lacking specific cell identification and isolation capabilities.

Innovation Solution

A system comprising a fluid delivery module, manifold, waste chamber, pump, magnet, heater, cell capture device, bubble removal module, processor, and data acquisition module that enables individual cell capture and analysis without antibody-coated chambers or biomagnetic tagging, facilitating real-time tracking and selective molecular testing, and maintaining cell viability through controlled fluid dynamics and magnetic separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If flow cytometry is used for cell identification and sorting, then cell observation is limited to a single instance, but the system cannot allow for multiple analyses of the same cell

Engineering Contradiction:
Improvemultiple cell analysis capabilityVSAvoidcell observation limitation
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The system segments the cell analysis process into distinct stages: cell capture in microfluidic chambers, individual cell imaging and characterization, and subsequent molecular analysis. This segmentation allows the same captured cell to be analyzed multiple times through different techniques (flow cytometry, microscopy, molecular assays) without destroying the cell, resolving the contradiction between single-instance observation and multi-analysis capability.

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If conventional microfluidic devices use antibody-coated substrates for cell selection, then specific antigen expression can be targeted, but non-expressing cells and cells with phenotypic transition cannot be captured

Engineering Contradiction:
Improvecell subpopulation sorting capabilityVSAvoidcell capture completeness
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The microfluidic device incorporates multiple capture mechanisms within a single system: antibody-coated chambers for antigen-specific cell selection, magnetic bead-coated chambers for magnetic separation, and uncoated chambers for size-based filtration. This multi-functional design enables capture of diverse cell populations including those expressing antigens, those with phenotypic transitions, and non-expressing cells, thereby achieving complete cell subpopulation sorting while maintaining reliability.

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

3Measurement precision

If conventional microfluidic devices capture cells using antibodies bound to the substrate, then cell-specific identification is achieved, but subsequent cell removal causes cell damage

Engineering Contradiction:
Improvecell identification accuracyVSAvoidcell damage during retrieval
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system introduces magnetic beads as intermediary carriers that temporarily bind to cells through magnetic attachment, allowing for gentle cell separation and removal. The magnetic beads serve as a mediating layer between the capture mechanism and the cell retrieval process, enabling precise cell identification through magnetic sorting while avoiding direct mechanical damage that would occur with conventional substrate-based antibody removal methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Object-affected harmful factors

If cellular filters are used for cell separation based on size, then significant cell damage is avoided, but the system suffers from clogging and does not allow for specific cell identification

Engineering Contradiction:
Improvecell viability maintenanceVSAvoidclogging and identification limitation
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The system segments the cell separation function across multiple parallel chambers with different selective mechanisms: some chambers use size-based filtration to maintain cell viability, while others use antibody coating or magnetic bead coating for specific cell identification. By dividing the separation function rather than relying on a single filter system, the design avoids clogging while enabling both viability maintenance and specific identification capabilities simultaneously.

Inventive Principle:
Principle #1Segmentation

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 efficient capture and analysis of cells with enhanced purification and viability, allowing for multiplex biomarker analysis and processing of unprocessed biological samples, such as whole blood, with reduced contamination and improved cell retrieval capabilities.

Implementation Method 1

The system can further comprise a magnet configured to separate captured cells from undesired sample materials

Methodology Applied
Scientific EffectMagnetic separation: Magnetism

Data Source

PatentUS20240307880A1System and method for capturing and analyzing cells
Publication Date: 2024.09.19 BIO RAD LABORATORIES INC
  • US20240307880A1 patent drawing
  • US20240307880A1 patent drawing
  • US20240307880A1 patent drawing

AI summary

A system for isolating cells in at least one of single-cell format and single-cluster format, comprising a reservoir, including a reservoir inlet and a reservoir outlet, configured to receive a biological sample and to receive at least one fluid, a manifold configured to receive and deliver the biological sample and the at least one fluid from the reservoir into a biological sample substrate, the manifold comprising a broad surface comprising a central region configured to receive the biological sample substrate, a set of openings configured to enable fluid flow transmission across the biological sample substrate, a manifold inlet configured to transmit flow from the reservoir the first subset of openings, a manifold outlet configured at a downstream end of the broad surface and coupled to the second subset of openings, the manifold outlet configured to transmit waste fluid from the manifold.