Dielectric Micro-Element Cell Separation After Cryopreservation
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Solution Overview
Problem
Existing methods for cryopreservation of cells and cell aggregates are inadequate in characterizing and separating viable from damaged cells, especially after thawing, due to uncontrolled stress and damage caused by cryoprotectants and unpredictable dielectrophoretic forces, which limits survival rates and quality post-thawing.
Innovation Solution
A device and method utilizing dielectric micro-elements with adjustable dielectric properties and alternating electric fields to manipulate and characterize cells, shifting DEP spectra to differentiate viable from damaged cells by their levitation heights in a controlled electric field.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cryoprotectants are used during freezing, then cell survival rate is improved, but cell stress and damage increase due to non-physiological effects and mechanical forces
Solution Approach 1:
The patent changes the physical-chemical parameters of the freezing process by controlling cooling rates and using specific electric field frequencies to counteract the harmful effects of cryoprotectants. The dielectrophoretic forces are tuned to compensate for mechanical stresses without requiring changes to the cryoprotectant composition.
Solution Approach 2:
The patent replaces mechanical characterization and separation methods with dielectrophoretic forces generated by alternating electric fields. This substitution allows for non-contact manipulation and separation of cells based on their dielectric properties, reducing additional mechanical stress on already vulnerable post-thaw cells.
2Reliability
If conventional freezing methods are used, then cell preservation is achieved, but characterization and separation of viable from damaged cells after thawing is insufficient
Solution Approach 1:
The patent uses dielectric spectral changes as an analog to color changes for cell characterization. Different cell states (viable, damaged, dead) exhibit distinct dielectric spectra at different frequencies, allowing optical-like detection and differentiation without physical contact or additional staining.
Solution Approach 2:
The patent introduces dielectric micro-elements as intermediaries that enhance the dielectric contrast between viable and damaged cells. These micro-elements act as mediators that amplify the subtle differences in cell dielectric properties, making characterization and separation more precise.
3Measurement precision
If multiple frequencies are used to shift DEP spectra for cell separation, then separation precision is improved, but device complexity increases
Solution Approach 1:
The patent employs periodic alternating electric fields at multiple frequencies to achieve cell separation. By cycling through different frequencies, the system can selectively manipulate different cell populations based on their dielectric resonance characteristics, achieving precise separation without requiring complex multi-electrode configurations.
Solution Approach 2:
The patent designs the electrode system to perform multiple functions: characterization, separation, and even cryopreservation support, all using the same alternating electric field apparatus. This multi-functionality reduces device complexity by eliminating the need for separate specialized equipment for each operation.
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
Enables rapid characterization and separation of cells post-thawing, reducing stress and improving survival rates by using dielectric micro-elements that adjust DEP spectra to distinguish viable from damaged cells, allowing for precise quality assessment and separation.
Implementation Method 1
the carrier element exhibits a weaker negative dielectrophoretic force in an alternating electric field with a first alternating frequency than in an alternating electric field with a second alternating frequency that is higher than the first alternating frequency
Data Source
Figure 1a~1c
Figure 2
Figure 3
AI summary
The invention relates to a device for characterizing, separating, multiplying and/or cryopreserving at least one biological cell, comprising at least one assembly of the at least one biological cell and at least one carrier element, wherein the carrier element exhibits a weaker negative dielectrophoretic force in an alternating electric field with a first alternating frequency than in an alternating electric field with a second alternating frequency that is higher than the first alternating frequency, and exhibits a stronger negative dielectrophoretic force at least in the alternating electric field with the second alternating frequency than an absolute value of a dielectrophoretic force of a single biological cell in the alternating electric field with the second alternating frequency, and the carrier element comprises at least two different materials.