Fluid Shear Stress Pulse System for Cancer Cell Enrichment

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Solution Overview

Problem

Cancerous cells exhibit resistance to fluid shear stress, making it difficult to selectively kill them while sparing normal cells, which is crucial for improving clinical diagnostic tests and therapeutic applications.

Innovation Solution

A fluid handling system that applies a plurality of pulses of fluid shear stress to a fluid sample using conduits with inner diameters less than 1000 μm, combined with a force delivery system and control system to repeatedly expose the sample to selected magnitudes and durations of fluid shear stress, selectively killing non-cancerous cells and enriching the sample with cancerous cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If fluid shear stress is applied to a fluid sample to selectively kill non-cancerous cells, then the sample becomes enriched in cancerous cells, but the process requires repeated exposure to achieve sufficient enrichment

Engineering Contradiction:
Improvecell enrichment purityVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The system applies fluid shear stress in repeated pulses rather than continuous exposure. The force delivery system delivers multiple discrete pulses of force to the fluid sample, with each pulse creating a burst of shear stress followed by a recovery period. This periodic application allows cumulative enrichment effect while maintaining system efficiency and preventing cell adaptation that would occur with continuous exposure.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The enrichment process is divided into multiple discrete steps or pulses rather than a single continuous process. Each pulse is a separate, controlled application of force that can be independently optimized. The system segments the overall enrichment task into manageable units that can be applied sequentially, allowing for better control over the enrichment quality and total processing time.

Inventive Principle:
Principle #1Segmentation

2Stress or pressure

If the inner diameter of conduits is reduced to increase fluid shear stress, then the stress magnitude increases, but the conduit dimensions become very small

Engineering Contradiction:
Improvefluid shear stress magnitudeVSAvoidconduit inner diameter
Core Design Contradiction:
Stress or pressureVSLength of moving object

Solution Approach 1:

The system uses dynamic force application rather than static pressure to generate shear stress. The force delivery system applies transient pulses of force that create high shear stress magnitudes during the pulse duration, then allows the system to return to a lower stress state. This dynamic approach allows achieving high shear stress without permanently maintaining small conduit dimensions or high pressure conditions.

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 imparts increased resistance to fluid shear stress in cancerous cells, allowing for their enrichment and improved characterization, enhancing diagnostic and therapeutic applications by selectively killing normal cells.

Implementation Method 1

a force delivery system mounted to the first sample chamber and configured to apply a force sufficient to push the fluid sample at a substantially constant flow rate from the first sample chamber through each of the conduits to the second sample chamber

Methodology Applied
Scientific EffectFluid shear stress: Shear Stress

Implementation Method 2

the force delivery system may be a gas delivery system configured to deliver gas to pressurize the sample chambers to a selected pressure

Methodology Applied
Scientific EffectGas pressurization: Pressurisation

Data Source

PatentUS10730046B2Fluid handling systems for application of fluid shear stress to a fluid sample
Publication Date: 2020.08.04 THE UNIVERSITY OF IOWA RESEARCH
  • US10730046B2 patent drawing
  • US10730046B2 patent drawing
  • US10730046B2 patent drawing

AI summary

A fluid handling system for applying a plurality of pulses of fluid shear stress to a fluid sample may comprise a first sample chamber; a second sample chamber; a plurality of conduits mounted between and in fluid communication with the first sample chamber and the second sample chamber; and a force delivery system mounted to the first sample chamber and configured to apply a force sufficient to push the fluid sample from the first sample chamber through each of the conduits at a substantially constant flow rate to the second sample chamber. The plurality of conduits may be arranged in series and separated by additional sample chambers or arranged such that the conduits are substantially parallel to one another. The force delivery system may be a gas delivery system or a linear drive assembly.