Tube and Float System for CTC Isolation

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Solution Overview

Problem

Detecting and isolating circulating tumor cells (CTCs) from whole blood is challenging due to their low frequency and the presence of numerous other cells, making it difficult to extract and analyze them effectively for cancer monitoring and treatment.

Innovation Solution

A tube and float system is used where the suspension is centrifuged with a float of specific gravity positioning it near the layer containing the target material, allowing nearly all target material to be trapped between the float and tube for detection, enumeration, and analysis, utilizing a separation filter to isolate and re-suspend the target material.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional centrifugation methods are used to separate particles in suspension, then separation occurs according to specific gravity, but target particles (CTCs) are lost among the large number of other cells due to low frequency (1-10 per mL)

Engineering Contradiction:
Improvedetection of target particlesVSAvoidconcentration of target particles
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent applies local quality by creating a specific region (the band) within the centrifuge tube where target particles are concentrated. The float device defines a localized zone with specific physical properties (density gradient) that selectively traps CTCs while allowing other cells to separate to different positions. This local concentration zone enables precise detection despite the low overall concentration of target particles in the entire sample volume.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The float device serves as an intermediary element that mediates the separation process. It creates a density gradient interface that acts as a selective barrier, allowing target particles to accumulate at the band while preventing them from being lost in the bulk sample. The float mediates between the centrifugal force field and the particle suspension, creating a controlled environment for target particle concentration and recovery.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If the float is positioned to expand the axial length of the target material layer, then nearly all target material is positioned between the float and tube for detection, but the device complexity increases

Engineering Contradiction:
Improveenumeration and characterization of target materialVSAvoidtube and float system structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The float device is designed to be self-adjusting and self-positioning during centrifugation. It automatically finds its equilibrium position based on the density gradient formed during centrifugation, eliminating the need for external control mechanisms or complex positioning systems. The float's buoyancy and geometry cause it to naturally expand the band to the optimal position where target particles accumulate, making the system self-regulating and reducing overall device complexity.

Inventive Principle:
Principle #25Self-service

3Quantity of substance

If separation filter is embedded in the tube cap to prevent passage of target material, then target material can be trapped and harvested, but the device complexity and operation difficulty increase

Engineering Contradiction:
Improveharvested target materialVSAvoidfluid removal and target material recovery
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The separation filter is pre-installed in the tube cap before the centrifugation process begins. This preliminary preparation ensures that when the band forms and target particles accumulate, they are automatically trapped by the pre-positioned filter as fluids are removed. The filter is already in place to perform its function, eliminating the need for additional steps to install or activate filtration during the recovery process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The filter serves to extract and remove fluids from the system while retaining target material. By selectively removing the supernatant and other layers through the filter, the system concentrates target particles on the filter surface, making them easily harvestable. The filter extracts the unwanted fluid components while leaving the valuable target material behind for recovery and analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

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

This method enables efficient separation, enumeration, and analysis of CTCs by positioning the target material between the float and tube, allowing for effective detection and characterization, even at low concentrations, facilitating cancer monitoring and treatment.

Implementation Method 1

the tube, float, and suspension are centrifuged together, causing the various materials suspended in the suspension to separate into different layers along the axial length of the tube according to their specific gravities

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Implementation Method 2

The float has a specific gravity that positions the float at approximately the same level as the layer expected to contain the target material when the tube, float and suspension are centrifuged together

Methodology Applied
Scientific EffectDensity gradient: Density Gradient

Data Source

PatentUS8445264B2Systems and methods for harvesting target particles of a suspension
Publication Date: 2013.05.21 RARECYTE INC
  • US8445264B2 patent drawing
  • US8445264B2 patent drawing
  • US8445264B2 patent drawing

AI summary

Tube and float systems and methods for isolating, enumerating, and harvesting target materials of a suspension are described. In one aspect, a tube and float system includes a filter embedded in a tube cap. The filter enables the passage of fluids but prevents the passage of the target materials. The tube and float system can be used to isolate and enumerate the target materials by centrifuging the tube and float system with the suspension to trap the target materials between the float and inner wall of the tube. Fluids above and below the float are poured off and a second fluid can be introduced to the tube to re-suspend the trapped target material. The second fluid can be poured through the filter in the cap to trap the target material against the filter. The target material can be enumerated and analyzed.