Magnetic Cell Isolation with Dynamic Field Gradient Washing
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Solution Overview
Problem
Current magnetic separation technologies face challenges in efficiently isolating rare cells from heterogeneous samples with high purity and low loss, particularly due to non-specific binding and inefficient enrichment processes, which hinder the development of rapid and cost-effective assays for early-stage cancer diagnosis.
Innovation Solution
A method involving the use of magnetic or magnetizable particles with specific surface components, combined with controlled adjustments of external magnetic field gradients and rotational speeds during incubation and washing steps, to minimize non-specific binding and enhance enrichment efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If magnetic particles are used for cell separation, then enrichment efficiency is improved, but non-specific binding increases causing loss of desired cells
Solution Approach 1:
The patent adjusts magnetic field gradient parameters dynamically during different process stages. A high gradient is applied during separation to maximize enrichment efficiency, while a low gradient is used during washing to minimize non-specific binding and cell loss. This parameter optimization resolves the contradiction between achieving high enrichment and minimizing desired cell loss.
Solution Approach 2:
The patent implements dynamic control of magnetic field strength and sample rotation speed throughout the separation process. The system transitions from static to dynamic operation, adjusting field gradients and rotation speeds based on process requirements. This dynamic approach allows high enrichment during separation while reducing non-specific binding during washing steps.
2Speed
If high magnetic field gradient is applied throughout the process, then separation speed is improved, but non-specific binding increases
Solution Approach 1:
The patent employs periodic variation of magnetic field gradient strength during the separation process. High gradients are applied intermittently during separation phases to maintain speed, while low gradients are applied during washing phases to reduce non-specific binding. This periodic action resolves the contradiction between separation speed and non-specific binding.
Solution Approach 2:
The system dynamically adjusts magnetic field gradient based on process stage requirements. During active separation, high gradients provide rapid separation speed. During washing and incubation phases, low gradients minimize non-specific binding. This dynamic adaptation resolves the contradiction between maintaining high separation speed and reducing harmful non-specific binding effects.
3Object-generated harmful factors
If sample rotation is performed during incubation, then non-specific binding is reduced, but enrichment efficiency decreases
Solution Approach 1:
The patent implements dynamic control of rotation speed based on process stage. During incubation phases, rotation is applied at optimized speeds to reduce non-specific binding while maintaining sufficient contact time for specific binding. During separation phases, rotation is adjusted to maintain enrichment efficiency. This dynamic adjustment resolves the contradiction between reducing non-specific binding and maintaining enrichment efficiency.
Solution Approach 2:
The system optimizes rotation speed parameters for different process stages. Moderate rotation speeds are applied during incubation to reduce non-specific binding without compromising enrichment efficiency. During separation, rotation parameters are adjusted to maintain high enrichment while minimizing non-specific binding. This parameter optimization resolves the contradiction between the two competing requirements.
4Force
If magnetic particles with large size are used, then magnetic moment is improved, but reactive surface area decreases
Solution Approach 1:
The patent optimizes magnetic particle size parameters to achieve the最佳 balance between magnetic moment and reactive surface area. Particles in the range of 100 nm to 4 μm provide sufficient magnetic moment for effective separation while maintaining adequate reactive surface area for ligand binding. This parameter optimization resolves the contradiction between magnetic moment and reactive surface area.
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 achieves near 5 log depletion of non-desired cells with minimal loss of desired cells, reducing assay time to a few minutes and enabling high-throughput isolation of rare cells, such as circulating tumor cells, suitable for marker-independent liquid biopsies and other diagnostic applications.
Implementation Method 1
subjected to an external magnetic field gradient throughout said adding, incubating, washing and separating steps
Implementation Method 2
A crystal grain size of at least 30 nm is required for the generation of the so called para-magnetic behavior. Such magnetic materials are often referred to as magnetic susceptible, magnetizable, or superparamagnetic
Data Source
AI summary
The present invention concern a method and a device for the isolation of non-magnetic cells from a heterogeneous sample solution containing biological material including desired and undesired cells. The method comprises the steps of: —adding magnetic or magnetizable particles to the sample, wherein said particles have sizes in a range from 100 nm to 4 μm and exhibit surface components which support specific association with target cells, wherein said target cells comprise are either said desired or said undesired cells; —decreasing said external magnetic field gradient; —incubating said sample solution with said magnetic particles to obtain a magnetized cell fraction; —washing said magnetized cell fraction using a washing solution to reduce non-specific binding; —increasing said external magnetic field gradient; —separating said magnetized cell fractionation of target cells from said sample; wherein said sample solution is subjected to an external magnetic field gradient throughout said adding, incubating, washing and separating steps, and wherein said sample solution is rotated at least during said adding, incubating and washing steps.