Microchamber Chip Void Ratio Control for Rare Cell Recovery

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Solution Overview

Problem

Existing methods for detecting rare cells, such as circulating tumor cells, from blood samples face challenges in achieving a high recovery ratio of cells in microchambers while maintaining industrial mass productivity and efficient production using molds, often resulting in false negatives due to high void ratios between microchambers.

Innovation Solution

A cell-spreading device with a microchamber chip having a void ratio not exceeding 5%, featuring a channel-forming frame with an inlet and outlet, where the microchambers are arranged to maximize cell retention with minimal void space, allowing for efficient cell spreading and retention during staining and washing processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If microchambers are arranged closely to minimize void space for high cell recovery ratio, then cell retention improves, but manufacturing difficulty increases due to mold removal constraints

Engineering Contradiction:
Improvecell recovery ratioVSAvoidmold removal
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention transitions from a 2D microchamber array to a 3D microchamber structure with multiple layers. By stacking multiple microchamber layers vertically, the device achieves high cell recovery ratio while maintaining manufacturability, as the 3D configuration allows for optimized void space distribution and easier mold removal compared to densely packed 2D arrangements.

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

2Reliability

If large amounts of cells are fed onto microarray chip surface, then detection sensitivity improves, but cell loss outside microchambers increases due to large space between microchambers

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcell loss
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The invention implements a nested structure where multiple microchamber layers are stacked vertically, with each layer containing microchambers that nest within the overall device structure. This nested 3D configuration maximizes the utilization of cell suspension volume, ensuring that cells fed onto the chip surface are efficiently captured across multiple layers, thereby reducing cell loss while maintaining high detection sensitivity.

Inventive Principle:
Principle #7Nested doll (Nesting)

3Reliability

If void ratio between microchambers is reduced to maximize cell enclosure, then cell retention improves, but device complexity increases

Engineering Contradiction:
Improvecell retentionVSAvoidmicrochamber arrangement
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention divides the microchamber structure into multiple discrete layers, with each layer containing a simplified 2D array of microchambers. This segmentation approach allows each layer to maintain a straightforward microchamber arrangement with manageable void ratios, while the overall 3D structure achieves high cell retention through the cumulative effect of multiple layers working together.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2871232B1Method for detecting rare cell
Publication Date: 2021.05.05 KONICA MINOLTA INC
  • EP2871232B1 patent drawingFigure 1(A)~2
  • EP2871232B1 patent drawingFigure 3
  • EP2871232B1 patent drawingFigure 4(A)~4(B)

AI summary

It is an object of the present invention to provide a cell-spreading device which has a high recovery ratio of cells when a cell suspension containing large amounts of various kinds of cells, such as blood, is spread onto the surface of a microchamber chip in the detection of rare cells from the cell suspension and which has a microchamber chip capable of being mass-produced by a mold. The cell-spreading device is a cell-spreading device (10) comprising at least a microchamber chip (1) having, on its surface, a microchamber (6) for retaining a cell, a channel-forming frame (2) that is united with the microchamber chip (1) so that a channel (5) may be formed on the microchamber (6), and an inlet (3) and an outlet (4) that are provided in order to allow a cell suspension to flow into the channel (5) and flow out therefrom, wherein the void ratio that is a ratio of a void (40) to a longitudinal width (2) of the microchamber chip (1) is not more than 5%.