Multidimensional Electrokinetic Cell Separation in High Conductance Samples
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Solution Overview
Problem
Conventional AC electrokinetic techniques, particularly dielectrophoresis (DEP), face limitations in efficiently separating and identifying rare cells, biomarkers, and nanoparticles in high conductance biological samples due to issues like sample dilution requirements, electrochemistry effects, and low throughput, which complicates clinical diagnostics and drug delivery processes.
Innovation Solution
The development of novel sample preparation and diagnostic systems that combine multidimensional AC electrokinetic and DEP forces with DC electrophoretic and microelectrophoretic techniques, using robust electrodes and porous structures to create separate high and low field regions within devices, allowing for efficient separation and analysis of cells, biomarkers, and nanoparticles under high ionic strength conditions without dilution or perturbation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional DEP techniques are used for separation, then separation capability is achieved, but sample dilution is required which reduces throughput and increases processing time
Solution Approach 1:
The device segments the electrode array into multiple independent sections that can be activated simultaneously, allowing parallel processing of multiple sample regions. This segmentation enables the system to handle undiluted samples with high cell concentrations without requiring sequential processing or dilution, thereby maintaining both separation precision and high throughput.
Solution Approach 2:
The patent transitions from conventional two-dimensional electrode arrays to a three-dimensional configuration with electrodes positioned above and below the sample chamber. This dimensional expansion creates multiple electric field zones that can process different sample regions simultaneously, eliminating the need for sample dilution while maintaining effective separation capability.
2Measurement precision
If conventional DEP techniques are used, then separation is achieved, but electrochemistry effects occur which compromise sample integrity
Solution Approach 1:
The patent introduces a dielectric layer as an intermediary between the electrodes and the sample. This intermediate layer prevents direct electrochemical reactions between the electrodes and sample components, eliminating harmful electrochemistry effects while still allowing the electric field to pass through and enable effective DEP separation.
Solution Approach 2:
The dielectric layer is designed with porous structure that allows the electric field to penetrate effectively while physically preventing direct contact between electrodes and sample. The porous material maintains electrical insulation properties to prevent electrochemistry while permitting field-mediated separation of cells and particles.
3Measurement precision
If conventional DEP techniques are used, then separation capability is maintained, but processing time increases due to low throughput
Solution Approach 1:
The electrode array is divided into multiple independently controllable sections that can be activated simultaneously. This segmentation allows parallel processing of multiple sample regions, reducing the total processing time while maintaining the separation precision of individual electrode pairs.
Solution Approach 2:
The patent enables continuous sample flow through the device with multiple electrode sections operating simultaneously. This continuous processing eliminates idle time between sample injections and allows uninterrupted separation, significantly reducing overall processing time while maintaining effective separation capability.
4Measurement precision
If sample dilution is performed to enable DEP, then separation can proceed, but sample volume requirements increase and rare cell detection efficiency decreases
Solution Approach 1:
The device segments the processing into multiple parallel electrode sections, each handling a portion of the undiluted sample. This segmentation allows the system to process the entire sample volume simultaneously without requiring dilution, maintaining the concentration of rare cells and minimizing the total sample volume needed for effective separation.
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 and high-throughput separation and identification of rare cells, biomarkers, and nanoparticles in undiluted biological samples, reducing sample processing time and minimizing sample perturbation, while avoiding electrochemistry-related issues, thus enhancing the sensitivity and specificity of clinical diagnostics.
Implementation Method 1
dielectrophoresis (DEP), which is an induced motion of particles produced by the dielectric differences between the particles and media in an AC electric field
Implementation Method 2
AC electroosmosis, which is surface fluid flow due to the surface charge on an electrode
Implementation Method 3
electrothermal flow, which is bulk flow in solution due to thermal gradients produced by the electric fields
Implementation Method 4
DC electrophoretic and microelectrophoretic techniques
Data Source
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AI summary
Devices and techniques are described that involve a combination of multidimensional electrokinetic, dielectrophoretic, electrophoretic and fluidic forces and effects for separating cells, nanovesicles, nanoparticulates and biomarkers (DNA, RNA, antibodies, proteins) in high conductance (ionic) strength biological samples and buffers. In disclosed embodiments, a combination of continuous and/or pulsed dielectrophoretic (DEP) forces, continuous and/or pulsed field DC electrophoretic forces, microelectrophoresis and controlled fluidics are utilized with arrays of electrodes. In particular, the use of chambered DEP devices and of a properly scaled relatively larger electrode array devices that combines fluid, electrophoretic and DEP forces enables both larger and/or clinically relevant volumes of blood, serum, plasma or other samples to be more directly, rapidly and efficiently analyzed. The invention enables the creation of "seamless" sample-to-answer diagnostic systems and devices. The devices and techniques described can also carry out the assisted self-assembly of molecules, polymers, nanocomponents and mesoscale entities into three dimensional higher order structures.