Holographic Cell Sorting for Label-Free CTC Isolation
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Solution Overview
Problem
Current methods for detecting and purifying Circulating Tumor Cells (CTCs) in liquid biopsies, such as blood samples, suffer from low efficiency and purity due to contamination with normal cells, and often require invasive procedures or cytotoxic labeling, which can damage cell characteristics and affect measurement validity.
Innovation Solution
A system and method utilizing holographic imaging and sorting, incorporating a holographic imaging module, cell sorting module, and control unit for real-time, label-free sorting of CTCs based on refractive index and morphological features, enabling automatic classification and sorting of CTCs without external labeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If filtration or magnetic beads and antibodies are used to isolate CTCs, then the percentage of CTCs is enriched, but the purity is not complete and normal cells remain contaminated
Solution Approach 1:
The patent replaces mechanical filtration and magnetic bead-based biological methods with optical field-based holographic imaging and dielectrophoresis. The holographic imaging module captures optical paths of cells, and the dielectrophoresis module uses non-uniform electric fields to manipulate and sort cells based on their electrical properties, achieving complete separation without mechanical contact or biological labeling.
Solution Approach 2:
The system changes the sorting parameter from size-based filtration or antibody-based magnetic separation to electrical property-based dielectrophoresis. By applying non-uniform electric fields, cells are sorted according to their polarizability and electrical characteristics, which differ between CTCs and normal cells, enabling complete purity separation.
2Measurement precision
If fluorescent markers or antibodies are attached to cells for identification, then cell specificity is improved, but cell characteristics are damaged and measurement validity is affected
Solution Approach 1:
The patent enables cells to serve themselves by utilizing their intrinsic optical and electrical properties for identification and sorting. The holographic imaging captures the cell's natural optical path, and the dielectrophoresis module responds to the cell's inherent electrical characteristics, eliminating the need for external fluorescent markers or antibodies that could damage the cell.
Solution Approach 2:
The system substitutes chemical/biological labeling methods with physical field-based detection. Instead of attaching fluorescent markers or antibodies, the holographic imaging module detects cells through their optical properties, and the dielectrophoresis module sorts them through their electrical properties, both of which are intrinsic to the cells and cause no damage.
3Quantity of substance
If conventional filtration or magnetic separation methods are used, then CTC enrichment is achieved, but the process is time-consuming and efficiency is low
Solution Approach 1:
The patent replaces slow mechanical filtration and magnetic separation processes with rapid optical field-based holographic imaging and electric field-based dielectrophoresis. The holographic imaging captures multiple cell parameters simultaneously, and the dielectrophoresis module rapidly manipulates cells using non-uniform electric fields, dramatically increasing processing speed and efficiency.
Solution Approach 2:
The system implements continuous flow processing where cells are continuously imaged by the holographic module and continuously sorted by the dielectrophoresis module. This eliminates the batch processing nature of conventional methods, maintaining continuous useful action throughout the isolation process and significantly improving productivity.
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
Achieves high purity and real-time sorting of CTCs with over 98% classification success and 69% sorting accuracy, preserving cell vitality and enabling personalized treatment options by analyzing genetic profiles of isolated CTCs.
Implementation Method 1
a holographic imaging module being configured and operable to image a flow of heterogeneous population of cell
Implementation Method 2
performing a holographic imaging of a flow of a heterogeneous population of cells to enable label-free quantitative imaging of the flow of cells
Implementation Method 3
combining dielectrophoresis and computer vision for precise and fully automated single-cell handling and analysis
Data Source
AI summary
The present invention relates to an automatic real-time label-free holography-activated sorting of the cell's technique. The technique provides high-discriminative power on the level of the individual cell. The technique includes rapid automated cell processing during cell visualization and flow, with high discriminative power on the level of the individual cell. The technique may be useful in detection of cancer and to identify different stages of oncogenesis.