Magnetic Rare Cell Sorting with Multi-Pass Flow Purification
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Solution Overview
Problem
Existing magnetic separator devices are inadequate for efficiently extracting and recovering rare cells from heterogeneous cell mixtures due to limitations in magnetic field strength, contamination risks, and non-specific binding of magnetic beads to non-target cells, which reduces the purity and recovery rate of target cells.
Innovation Solution
A method involving multiple passes through a column-free continuous flow magnetic separator device with adjustable flow rates and mechanical agitation to enhance magnetic field exposure and hydrodynamic forces, allowing for higher purity and recovery of magnetically labeled rare cells by depositing them on the conduit wall and selectively removing non-target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If magnetic beads are used to label target cells for magnetic sorting, then the target cells can be magnetically labeled and separated, but the magnetic beads may bind non-specifically to non-target cells, reducing the purity of the sorted cells
Solution Approach 1:
The patent divides the magnetic sorting process into multiple sequential passes through the magnetic separator device. Each pass further purifies the cell population by removing additional non-target cells that bound magnetic beads non-specifically in previous passes. This segmentation of the sorting process into iterative steps progressively enhances purity while managing non-specific binding effects.
Solution Approach 2:
The patent adjusts the flow rate parameter during different passes through the magnetic separator. By varying flow rates, the system optimizes the balance between magnetic separation efficiency and hydrodynamic forces, allowing for better control of non-specific binding and improved overall purity of the sorted rare cells.
2Productivity
If conventional magnetic separator devices are used, then the device structure is simple, but the magnetic field strength is insufficient and contamination risks increase, reducing the efficiency of rare cell extraction
Solution Approach 1:
The patent employs multiple sequential magnetic separation passes instead of a single pass through a conventional device. This segmented approach achieves higher extraction efficiency and reduces contamination by progressively purifying the cell population, effectively replacing the need for a single complex high-field device with multiple uses of a simpler device.
Solution Approach 2:
The patent implements continuous flow through the magnetic separator device during each pass, maintaining continuous magnetic separation action. This continuous operation enhances extraction efficiency compared to batch processing, while the sequential pass structure ensures thorough purification without requiring complex device modifications.
3Productivity
If the flow rate is increased to improve processing speed, then the throughput increases, but the magnetic field exposure time decreases, reducing the purity of separation
Solution Approach 1:
The patent segments the separation process into multiple passes, allowing each pass to operate at optimized flow rates. This segmentation enables the system to achieve both high throughput and high purity by distributing the separation task across multiple stages rather than requiring a single high-speed pass that would compromise separation quality.
Solution Approach 2:
The patent dynamically adjusts flow rates between different passes through the magnetic separator. By varying flow rates according to the specific requirements of each pass, the system optimizes the balance between throughput and separation purity, allowing faster flow rates in later passes when the cell population is already more purified.
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 method significantly increases the purity and recovery rate of rare cells, achieving up to 97.17% purity and 83.4% recovery of CD34+ hematopoietic stem cells, demonstrating improved efficiency over conventional methods.
Implementation Method 1
Each of the antibody-conjugated magnetic beads 54 includes a magnetic entity 56 conjugated with one or more antibodies or other ligands 58, such as peptides and aptamers, that correspond to the surface markers 52. After an incubation period, the magnetic beads 54 may be directly attached to the cell 50 via the antigen-antibody interaction to form a magnetically labeled cell
Implementation Method 2
a magnetic particle may exhibit superparamagnetism as its size is reduced to tens of nanometers. In a sufficiently small ferromagnetic (e.g., iron) or ferrimagnetic (e.g., iron oxide) nanoparticle that exhibits superparamagnetism, magnetization can randomly flip direction under the influence of temperature. The typical time period between two such consecutive flips is known as the Neel relaxation time, or simply the relaxation time.
Implementation Method 3
During a cell sorting process, the magnetic nanoparticles of the magnetically labeled cells are first magnetized by sufficiently high magnetic field generated by a magnetic separator device and then attracted to regions of high magnetic field gradient.
Implementation Method 4
flowing the first fluid sample unimpeded through a first conduit of a first magnetic separator device at a first flow rate to deposit a second mixture of non-target and magnetically labeled target cells having a higher purity of the magnetically labeled target cells than the first mixture of non-target and magnetically labeled target cells on a conduit wall of the first conduit
Implementation Method 5
A method involving multiple passes through a column-free continuous flow magnetic separator device with adjustable flow rates and mechanical agitation to enhance magnetic field exposure and hydrodynamic forces, allowing for higher purity and recovery of magnetically labeled rare cells by depositing them on the conduit wall
Data Source
AI summary
A method for magnetically sorting rare cells including the steps of (a) flowing a first fluid sample, which contains a first mixture of non-target and magnetically labeled target cells, unimpeded through a conduit of a magnetic separator device at a first flow rate to deposit on a conduit wall a second mixture of non-target and magnetically labeled target cells having a higher purity of the magnetically labeled target cells; (b) recovering the second mixture from the conduit wall by eluting with a buffer fluid to form a second fluid sample; repeating steps (a) and (b) at least one more time using the second fluid sample and a second flow rate to produce a third fluid sample containing a third mixture of non-target and magnetically labeled target cells having a higher purity than the second mixture, wherein the second flow rate is greater than the first flow rate.