Fritted Column Cell Purification Throughput

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Solution Overview

Problem

Current methods for purifying cells, such as magnetic bead technologies and microfluidic devices, are slow and inefficient, resulting in low throughput and poor cell recovery, especially for rare circulating tumor cells, which are difficult to capture and process effectively.

Innovation Solution

The use of a fritted column with a bed of medium that allows bidirectional flow, enabling high-speed cell purification and recovery of viable cells by capturing cells on a medium within the column and eluting them using an eluent, which is faster and more efficient than existing methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If magnetic bead methods are used for cell capture, then cell separation can be achieved, but the process is slow and has low throughput

Engineering Contradiction:
ImprovethroughputVSAvoidprocessing time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent replaces magnetic field-based cell separation with a mechanical filtration system using a fritted glass column. Cells are separated based on size exclusion through the frit structure, eliminating the need for magnetic beads and external magnetic fields, thereby significantly increasing throughput and reducing processing time

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs a fritted glass column with porous structure that allows differential passage of cells based on their size. The frit pores are designed to retain larger cells while allowing smaller particles and fluid to pass through, enabling rapid mechanical separation without magnetic components

Inventive Principle:
Principle #31Porous materials

2Measurement precision

If microfluidic devices are used for cell purification, then rare cells can be captured, but the flow rate must be very slow making processing time-consuming

Engineering Contradiction:
Improvecell capture efficiencyVSAvoidprocessing speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent segments the cell separation process into distinct functional zones within the fritted column structure, including an accumulation zone where rare cells are concentrated and a separation zone where they are isolated from the flow. This segmentation allows efficient capture of rare cells at higher flow rates compared to uniform microfluidic channels

Inventive Principle:
Principle #1Segmentation

3Productivity

If column frit is used to allow liquid flow through, then throughput increases, but cells may be trapped, damaged or killed by the frit

Engineering Contradiction:
ImprovethroughputVSAvoidcell integrity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent optimizes the frit pore size parameters to be sufficiently large to prevent cell trapping and damage while maintaining effective separation. The frit structure is designed with controlled porosity that allows liquid and small particles to pass freely while retaining intact cells, thus preserving cell viability and integrity during high-throughput processing

Inventive Principle:
Principle #35Parameter changes

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 allows for the rapid purification of cells, including viable and cancer cells, with high purity and efficiency, capable of processing samples in under an hour, significantly improving throughput and maintaining cell integrity and viability.

Implementation Method 1

cells are captured on the medium within the column

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

Cells are recovered by passing an eluent through the column

Methodology Applied
Scientific EffectDesorption: Desorption

Data Source

PatentUS10307693B2Methods for purifying biological cells
Publication Date: 2019.06.04 GJERDE DOUGLAS T
  • US10307693B2 patent drawing
  • US10307693B2 patent drawing
  • US10307693B2 patent drawing

AI summary

This invention relates to devices and methods for purifying biological cells. For example, viable tumor, stem, immune and sperm cells can be purified from a complex biological sample using a pipette tip column. Methods of the invention can aid research, diagnosis and treatment of cancer.