Microsieve Diagnostic Device for Single Cell Isolation

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Solution Overview

Problem

Current filtration membranes used in diagnostic devices face challenges such as high flow resistance, non-wettable surfaces, and inability to capture cells at zero pressure, limiting their practicality for single cell separation and analysis, especially in applications requiring low pressure conditions like in vitro diagnostics.

Innovation Solution

A microsieve diagnostic device with a micromachined wettable microsieve and an absorbing pad allows fluid passage at zero pressure, enabling the capture and distribution of single cells, and includes a fluidic pathway for sample reagents and waste, along with a reagent reservoir for subsequent analysis using fluorescence microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If conventional filtration membranes are used, then cell capture function is provided, but high flow resistance prevents operation at zero pressure

Engineering Contradiction:
Improveoperating pressureVSAvoidflow rate
Core Design Contradiction:
Stress or pressureVSProductivity

Solution Approach 1:

The patent employs a micromachined microsieve with precisely engineered porous structure. The microsieve features uniform pores with controlled size and distribution, creating optimized flow pathways that minimize resistance while maintaining effective cell capture. This porous structure allows the device to operate at zero pressure with adequate flow rate, resolving the contradiction between low operating pressure and productivity.

Inventive Principle:
Principle #31Porous materials

2Reliability

If conventional non-wettable membranes are used, then structural stability is maintained, but inability to capture cells at zero pressure limits diagnostic application

Engineering Contradiction:
Improvecell capture efficiencyVSAvoidpre-wetting requirement
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent modifies the surface properties of the microsieve by changing its wettability parameter. The micromachined microsieve is designed with surface characteristics that promote wetting, enabling the membrane to become saturated with fluid and capture cells efficiently at zero pressure without requiring manual pre-wetting steps, thus improving ease of operation while maintaining reliability.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If manual cell seeding into microwells is used, then single cell distribution is achieved, but dilution causes low percentage of filled wells

Engineering Contradiction:
Improvesingle cell positioning accuracyVSAvoidnumber of captured cells
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent employs a flow-based self-organizing mechanism where cells are automatically distributed into microwells through controlled fluid flow. The microsieve structure guides cell suspension through channels that direct single cells into individual wells without requiring manual manipulation or extreme dilution. This self-service approach achieves both high single-cell positioning accuracy and maximizes the number of filled wells by utilizing the natural flow and sedimentation processes.

Inventive Principle:
Principle #25Self-service

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 device effectively captures and analyzes single cells with high efficiency, reducing the risk of multiple cells entering the same well, allowing for precise analysis and interrogation of captured cells without the need for pre-wetting or pressurization, enhancing diagnostic capabilities in various medical and scientific applications.

Implementation Method 1

a micromachined microsieve and absorbing pad provide a filtration membrane system for capturing individual cells

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

The sample liquid is filtered through the microsieve which has a low flow resistance allowing for high flow rates

Methodology Applied
Scientific EffectPhysical filtration: Filter (physical)

Data Source

PatentUS9975125B2Microsieve diagnostic device in the isolation and analysis of single cells
Publication Date: 2018.05.22 VYCAP
  • US9975125B2 patent drawing
  • US9975125B2 patent drawing
  • US9975125B2 patent drawing

AI summary

A micro well plate is described for capturing and distributing single cells in individual wells is described, wherein at least one individual well is provided with a bottom plate having at least one pore to pass sample liquid, such that if one object or cell of interest is collected on the bottom plate of the well, the sample flow rate through that particular well is significantly reduced, minimizing the possibility that multiple cells or objects of interest entering the same well. The presented invention is particularly suited for obtaining single cells and/or microorganisms suspended in fluid samples for subsequent detailed interrogation.