Microfluidic Magnetophoretic Separation for Basophil Isolation
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Solution Overview
Problem
Current methods for isolating basophils from whole blood are inefficient, with low recovery and purity rates, and require large blood volumes and extensive manual processing.
Innovation Solution
A magnetophoretic separation device (MSD) that applies varying magnetic field strengths to magnetically tagged cells, using immunomagnetic negative selection to maintain target cells in their native state, allowing for efficient isolation from low volumes of whole blood without the need for careful alignment or extensive manual handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional immunomagnetic negative selection methods are used, then basophil purity can be improved, but recovery rate deteriorates due to multiple manual steps and centrifugation
Solution Approach 1:
The patent replaces manual mechanical operations (pipetting, centrifugation) with an automated magnetophoretic separation system. The microfluidic device uses magnetic field gradients to automatically separate magnetically labeled non-basophils from the cell suspension, eliminating the need for repeated manual centrifugation steps while maintaining high purity and improving recovery rate.
Solution Approach 2:
The patent introduces magnetic nanoparticles as an intermediary to label non-basophils for selective removal. By coating magnetic beads with antibodies against non-basophil markers (CD3, CD14, CD16), the system enables automated magnetic separation, replacing manual density gradient methods and improving both purity and recovery through automated magnetophoretic separation.
2Manufacturing precision
If multiple manual pipetting and centrifugation steps are performed, then separation purity can be improved, but processing time deteriorates
Solution Approach 1:
The patent implements continuous automated magnetophoretic separation through the microfluidic device. The system continuously processes cell suspensions through channels with integrated magnets, maintaining continuous magnetic field exposure and flow, thereby eliminating the intermittent processing nature of manual centrifugation steps and reducing total processing time while maintaining high purity.
Solution Approach 2:
The patent performs preliminary magnetic labeling of non-basophils before separation. By pre-coating magnetic nanoparticles with antibodies and incubating them with the cell suspension, the system prepares the sample for automated separation, eliminating the need for repeated labeling and centrifugation cycles required in conventional methods.
3Quantity of substance
If large volumes of whole blood are processed, then sufficient target cells can be obtained, but device complexity and manual handling requirements deteriorate
Solution Approach 1:
The patent segments the blood processing into distinct automated stages: whole blood input, magnetic nanoparticle labeling, magnetophoretic separation, and purified basophil output. The microfluidic device is divided into channels with integrated magnets at specific positions, enabling automated segmentation of the separation process and reducing manual handling while processing variable blood volumes.
4Manufacturing precision
If density gradient centrifugation is used, then basophil isolation can be achieved, but recovery and purity rates deteriorate due to cell loss in gradient layers
Solution Approach 1:
The patent replaces density gradient centrifugation with magnetophoretic separation in a microfluidic system. Instead of relying on density differences that cause cell loss in gradient layers, the system uses magnetic field gradients to selectively capture magnetically labeled non-basophils, maintaining high recovery and purity rates while achieving effective basophil isolation.
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
The MSD achieves higher purity and recovery rates of basophils with reduced processing time and volume requirements, maintaining the cells in their native state for downstream assays.
Implementation Method 1
A magnetophoretic separation device (MSD) that applies varying magnetic field strength to flowing magnetically tagged cells
Implementation Method 2
spacing of the one or more magnetic flux concentrators relative to the single magnet or magnetic array and the one or more fluidic conduits is selected to produce a target magnetophoretic gradient profile, wherein magnetophoretic force varies along the length of the one or more fluidic conduits
Implementation Method 3
using immunomagnetic negative selection to maintain target cells in their native state
Data Source
AI summary
Devices, methods, and kits are provided for isolating a target cell from a fluid sample. In particular, a magnetophoretic separation device is provided that applies varying magnetic field strength to flowing magnetically tagged cells. Immunomagnetic negative selection of target cells is used to maintain target cells in their native, unlabeled state. The magnetophoretic separation device is suitable for isolating cells from low volumes of whole blood, which provides an advantage over in-bulk methods that require larger starting volumes of blood. A computer implemented method is also provided for producing target magnetophoretic profiles along the path through which cells travel through a fluidic conduit in the device that is adaptable to a variety of form factors.