Particle Separator Using Magnetic Forces for High-Purity Cell Nuclei
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Solution Overview
Problem
Existing methods for isolating and concentrating particles, particularly cell nuclei, are inefficient, time-consuming, and often damage cells due to high mechanical forces, especially in low-volume or fragile samples, and fail to effectively separate nuclei from debris.
Innovation Solution
A method using wheat germ agglutinin (WGA) for lysing cells and a fluidic device with magnetic components to separate cellular nuclei from contaminants without centrifugation, employing paramagnetic compounds and isolation particles to manipulate particle movement through magnetic forces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If centrifugation is used to concentrate cells, then cell concentration is improved, but cell damage and activation occur due to high mechanical forces
Solution Approach 1:
The patent replaces the mechanical centrifugation system with a magnetic field-based separation system. Paramagnetic beads are used to label cells, and magnetic fields exert forces on these beads to concentrate and separate cells without applying high mechanical centrifugal forces that cause cell damage and activation.
Solution Approach 2:
The patent introduces paramagnetic beads as intermediary agents that bind to cells. These beads serve as mediators between the magnetic field and the cells, allowing indirect manipulation of cell position and concentration through magnetic forces rather than direct mechanical force application.
2Quantity of substance
If traditional nuclei purification methods are used, then nuclei isolation is achieved, but purity and yield are poor and the process is time-consuming
Solution Approach 1:
The patent replaces traditional mechanical and chemical purification methods with magnetic field-based separation. By labeling nuclei or cell components with paramagnetic materials, the system uses magnetic fields to selectively separate nuclei from debris and contaminants, achieving high purity and yield in a time-efficient manner.
Solution Approach 2:
The patent changes the physical parameters of the separation process by utilizing magnetic field strength and direction as controllable parameters. This allows precise control over the separation process to optimize both nuclei yield and purity, overcoming the limitations of traditional methods.
3Quantity of substance
If bulk separation techniques are used for rare or low volume samples, then particle separation is achieved, but sample wastefulness and laboriousness increase
Solution Approach 1:
The patent applies magnetic field-based separation to rare or low volume samples, replacing bulk mechanical separation techniques. The magnetic field can be applied locally and with precision to small sample volumes, enabling efficient separation without requiring large sample quantities and reducing waste.
Solution Approach 2:
The patent transitions from three-dimensional bulk centrifugation to a more controlled two-dimensional or one-dimensional magnetic field application. This dimensional change allows for more precise and volume-efficient separation, particularly beneficial for rare or low volume samples.
4Quantity of substance
If centrifugation is used for particle separation, then particle concentration is improved, but precise conditions for particle stability become challenging
Solution Approach 1:
The patent substitutes mechanical centrifugation with magnetic field-based separation, which operates under different physical principles. This substitution allows for more precise control over separation conditions, as magnetic fields can be finely tuned without the extreme forces and temperature changes required for centrifugation, thereby maintaining particle stability.
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
Enhances the purity and yield of isolated cell nuclei, reducing contamination and mechanical stress, while allowing for efficient separation and concentration of live cells and nuclei from debris.
Implementation Method 1
lysing the cells in a nuclei isolating buffer; wherein the nuclei isolating buffer comprises wheat germ agglutinin (WGA)
Implementation Method 2
employing paramagnetic compounds and isolation particles to manipulate particle movement through magnetic forces
Data Source
AI summary
The present invention relates generally to the concentration of particulate containing samples, such as cells or biomolecules, in order to isolate such particles within a medium and to isolate particle depleted medium. In some embodiments, the present invention relates generally to the separation and/or concentration of cell nuclei from nuclear debris and dead cells.