Density-Based Rare Cell Isolation Using Depletion Agents

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Solution Overview

Problem

Current methods for analyzing suspensions, such as blood samples, are inefficient in detecting and isolating rare materials like circulating tumor cells due to their low concentration, making it difficult and time-consuming to accurately detect and analyze them.

Innovation Solution

A system and method involving a collector and processing vessel system that uses density-based separation by adding depletion agents to separate target materials from non-target materials, utilizing a collector with a cannula and processing vessel to funnel and isolate the target material through centrifugation, and a clearing fluid to further separate and collect the target material.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional blood film analysis is used to detect rare cells, then the method is simple and inexpensive, but the detection accuracy is extremely low due to the rarity of target cells among billions of background cells

Engineering Contradiction:
Improvedetection accuracyVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the blood sample into multiple density-based fractions through sequential centrifugation steps. Depletion agents are added to create density gradients that separate different cell types, isolating rare target cells from the overwhelming background of common blood cells. This segmentation transforms a single complex detection problem into multiple simpler separation stages.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces depletion agents as intermediary substances that mediate the separation process. These agents modify the density characteristics of non-target cells, enabling their removal from the sample. The intermediaries facilitate the isolation of rare target cells by creating density-based distinctions between target and non-target materials.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If sequential density fractionation with depletion agents is used, then the isolation accuracy of rare cells is dramatically improved, but the process complexity and time required increase significantly

Engineering Contradiction:
Improveisolation accuracyVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary density-based depletion of non-target cells before final target cell isolation. By removing common blood cells and other non-target materials in advance through controlled centrifugation and depletion agent addition, the subsequent detection and isolation of rare target cells becomes more efficient and accurate, reducing overall processing time despite the additional steps.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs multiple sequential depletion steps that may remove more material than strictly necessary, ensuring complete elimination of interfering non-target cells. This excessive action in the depletion phase prevents contamination of the final target cell isolate, improving overall isolation accuracy while managing processing time through optimized centrifugation parameters.

Inventive Principle:
Principle #16Partial or excessive action

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 approach enables efficient and accurate isolation of target materials from suspensions, overcoming the challenges of low concentrations by effectively separating and collecting rare cells like CTCs, improving detection and analysis efficiency.

Implementation Method 1

density-based separation by adding depletion agents and centrifugation to isolate target materials from suspensions

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Implementation Method 2

A first depletion agent may be added to a vessel that contains the sample to remove or change the density of a non-target material

Methodology Applied
Scientific EffectDensity change:

Data Source

PatentUS9541481B2Apparatus, system, and method for collecting a target material
Publication Date: 2017.01.10 RARECYTE INC
  • US9541481B2 patent drawing
  • US9541481B2 patent drawing
  • US9541481B2 patent drawing

AI summary

This disclosure is directed to an apparatus, system and method for retrieving a target material from a sample. A first depletion agent may be added to a vessel that contains the sample to change the density of a non-target material.