Patterned Microchannel Posts for Rare Cell Capture Uniformity

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Solution Overview

Problem

Current methods for isolating rare cells from bodily fluids are inefficient and lack effective techniques for uniform separation, particularly in complex cell populations, which hinders their use in disease diagnosis and research.

Innovation Solution

A microflow apparatus with a microchannel device featuring a collection region with transverse posts arranged in an irregular pattern, disrupting straight-line flow and promoting swirling, combined with sequestering agents attached to the posts and surfaces, captures target biomolecules through flow disruption and gravity-induced force vectors, enhancing cell separation efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cells are separated using conventional methods, then separation can be achieved, but the efficiency is low and uniform separation is difficult in complex cell populations

Engineering Contradiction:
Improvecell separation efficiencyVSAvoiduniformity of separation
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The microchannel is segmented into distinct functional regions: an injection region for sample introduction, a separation region with patterned posts for cell separation, and a collection region for sorted cell collection. This spatial segmentation allows each region to perform its specific function optimally, achieving both high efficiency and uniformity in cell separation

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The separation region features locally differentiated properties with posts of varying heights (e.g., 50 μm, 100 μm, 150 μm) arranged in specific patterns. This local variation in post height creates different flow resistance zones that selectively guide different cell types to different collection outlets, ensuring uniform separation while maintaining high processing efficiency

Inventive Principle:
Principle #3Local quality

2Reliability

If microchannel devices are used for cell separation, then separation capability is improved, but device complexity increases

Engineering Contradiction:
Improveseparation capabilityVSAvoidmicrochannel structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Multiple separation mechanisms are merged into a single integrated microchannel device: hydrodynamic flow, gravitational settling, and selective adhesion to posts. The patterned posts serve multiple functions simultaneously as flow obstacles, adhesion sites, and sorting elements, reducing the need for multiple separate components while maintaining high separation capability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The device transitions from two-dimensional planar separation to three-dimensional separation by incorporating posts with varying heights throughout the channel depth. This vertical dimensionality allows cells at different depths and positions to be separated simultaneously, enhancing separation capability without proportionally increasing device footprint or complexity

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 apparatus achieves high efficiency in capturing target cells by disrupting streamlined flow and utilizing gravity, resulting in effective separation and collection of rare cells from bodily fluids, with up to 97% capture efficiency demonstrated in experiments.

Implementation Method 1

interrupting straight-line flow and streamlined flow of liquid through the collection region by an irregular pattern of posts

Methodology Applied
Scientific EffectFlow disruption: Turbulence

Implementation Method 2

force vectors that result from gravity, which vectors are aligned at an acute angle to the lower surface of the collection region

Methodology Applied
Scientific EffectGravity: Gravitation

Implementation Method 3

sequestering agents that will bind with target biomolecules

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentUS20240151234A1Cell separation using microchannel having patterned posts
Publication Date: 2024.05.09 PLUS THERAPEUTICS INC
  • US20240151234A1 patent drawing
  • US20240151234A1 patent drawing
  • US20240151234A1 patent drawing

AI summary

A micro flow device for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts. The posts are spaced across the width of an expanded collection chamber region in the flow path, extending between the upper and lower surfaces thereof; they have rectilinear surfaces, being curved in cross-sections, e.g. circular or tear-drop shaped, and are randomly arranged so as to disrupt streamlined flow. The device is oriented so that its lower surface is aligned at about 45° to the horizontal. Sequestering agents, such as Abs, which are attached to surfaces of the collection region via a hydrophilic coating, preferably a permeable hydrogel containing isocyanate moieties, are highly effective in capturing cells or other targeted biomolecules while the remainder of the liquid sample exits horizontally.