Centrifugal Float Tube System for CTC Isolation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for detecting and isolating target components from suspensions, such as circulating tumor cells in blood samples, are inefficient and costly due to the low numbers of these cells in a vast background of other cells, making it difficult to accurately analyze them using existing techniques.

Innovation Solution

A tube and float system is used where the suspension is centrifuged with a float of specific gravity matching the target analyte, allowing the analyte to separate and be trapped within the float, which can then be isolated and analyzed using techniques like nucleic acid or protein microarrays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used to find target cells in blood samples, then the detection process can be performed with standard equipment, but the detection accuracy is extremely low due to the vast background of normal cells (40-50 billion cells) containing only a few target cells (as few as 3 CTCs)

Engineering Contradiction:
Improvedetection accuracyVSAvoidcomplexity of separation system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The blood sample is segmented into multiple layers based on density during centrifugation. The float divides the separation space into distinct zones, with the target analyte layer being trapped between the float and tube wall. This segmentation allows selective access to the low-abundance target cells by physically isolating them in a specific layer, dramatically improving detection accuracy from finding 3 CTCs in 50 billion cells to concentrating them in a accessible layer.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The float acts as an intermediary device with specific gravity matching the target analyte layer. It mediates the separation process by positioning itself at the density interface, creating a physical barrier that traps the target layer containing the rare CTCs. This intermediary structure enables selective isolation without requiring complex automated systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If manual isolation and extraction techniques are used for target components, then the process can be performed with simple equipment, but the time required is extremely long and the cost is very high

Engineering Contradiction:
Improveisolation efficiencyVSAvoidtime for detection and isolation
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The separation and concentration of target analytes is performed preliminarily during the centrifugation step itself. The float is positioned in advance with specific gravity matching the target layer, so that during routine centrifugation, the target cells are automatically concentrated and trapped in the accessible layer between the float and tube wall. This preliminary concentration eliminates the need for time-consuming manual isolation steps afterward, dramatically improving productivity.

Inventive Principle:
Principle #10Preliminary action

3Manufacturing precision

If density-based centrifugation is used to separate suspension components, then the separation can be achieved based on specific gravity differences, but the target analyte layer is difficult to access and isolate after separation

Engineering Contradiction:
Improveseparation precisionVSAvoidease of analyte access
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

The centrifugation separation space is segmented by the float into distinct accessible and inaccessible zones. The target analyte layer is trapped in the accessible zone between the float and tube wall, while other layers remain in inaccessible zones. This segmentation maintains high separation precision based on density differences while simultaneously making the target layer easily accessible for withdrawal and analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The float structure extracts or removes the target analyte layer from the bulk suspension by trapping it in a defined space between the float and tube wall. This extracted layer can then be easily accessed and withdrawn for analysis, solving the problem of difficult access that normally follows density-based separation.

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 and accurate isolation of target analytes from suspensions, reducing the time and cost associated with detecting low-abundance components like circulating tumor cells, allowing for more effective analysis and diagnosis.

Implementation Method 1

the tube, float and sample are centrifuged, causing the constituent components of 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

separate into different layers along the axial length of the tube according to their specific gravities

Methodology Applied
Scientific EffectDensity gradient: Density Gradient

Implementation Method 3

utilizing a permeable portion with selective permeability to trap the target analyte while preventing non-target components from entering

Methodology Applied
Scientific EffectSelective permeability: Semipermeable Membrane

Data Source

PatentUS8632736B2Float and tube system for separating a suspension with an internal trap
Publication Date: 2014.01.21 RARECYTE INC
  • US8632736B2 patent drawing
  • US8632736B2 patent drawing
  • US8632736B2 patent drawing

AI summary

This disclosure is directed to systems for separating a target analyte from a suspension. A suspension is added to a tube. A float is also added to the tube, and the tube, float, and suspension are centrifuged together, causing the constituent components of the suspension to separate into different layers along the axial length of the tube according to their specific gravities. The float has a specific gravity that positions the float at approximately the same level as a layer containing the target analyte, when the tube, float and sample are centrifuged. Prior to isolation, the material may be located between an outer surface of the float and an inner surface of the tube, or within a central bore that extends longitudinally through the float. The target analyte may then be drawn into a compartment within the float, thereby isolating the target analyte from the other suspension constituents.