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US 12,584,845 B2Granted
System and method thereof for real-time automatic label-free holography-activated sorting of cells
AssigneesRamot at Tel-Aviv University Ltd., Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e. V.
InventorsNatan Tzvi Shaked, Itay Barnea, Matan Dudaie, Noga Nissim, Michael Kirschbaum, Marten Tobias Gerling
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Abstract
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.
Claims17
A method for use in classification and sorting of certain type of cells in body fluids comprising:
- performing a holographic imaging of a heterogeneous population of cells during a flow of said cells and obtaining image data indicative of single-cell holograms of said cells, to enable label-free quantitative imaging of the flow of cells;
- automatically processing said image data to identify a certain type of cells during the flow, said automatically processing comprising:
- reconstructing optical path delay (OPD) maps from said image data, for each cell individually;
- automatically processing said OPD maps and identifying a certain type of cells, said automatically processing utilizing a trained classifier performing real-time machine learning classification to extract, from each OPD map, a plurality of 2D and 3D morphological and quantitative features of the heterogeneous population of cells, thereby identifying the certain type of cells within said heterogenous population of cells;
- and
- activating automatic sorting of the certain type of cells during said flow of the cells, thereby obtaining a real-time, automatic, label-free holography-activated sorting of the cells.
3 more elements
A system for use in classification and sorting certain type of cells in body fluids, the system comprising:
- a holographic imaging module being configured and operable to image a flow of heterogeneous population of cells and provide image data indicative of single-cell holograms of said cells;
- a cell sorting module being configured as a microfluidic module and operable to sort the flow of cells;
- and
- a control unit being configured and operable to receive from said holographic imaging module the image data being indicative of the single-cell holograms of said cells single-cell holograms of said cells during flow thereof and automatically process the image data and identify a certain type of cells during the flow;
- and upon identification of a certain type of cells activating said cell sorting module, to thereby enable real-time, automatic, label-free holography-activated sorting of the cells;
- wherein said control unit is configured and operable to perform said automatic processing of the image data as follows:
- reconstructing optical path delay (OPD) maps from said image data, for each cell individually;
- automatically processing said OPD maps and identifying a certain type of cells, said automatically processing utilizing a trained classifier performing real-time machine learning classification to extract, from each OPD map, a plurality of 2D and 3D morphological and quantitative features of the heterogeneous population of cells, thereby identifying the certain type of cells within said heterogenous population of cells;
- and
- activating automatic sorting of the certain type of cells during said flow of the cells, thereby obtaining a real-time, automatic, label-free holography-activated sorting of the cells.
7 more elements
A method comprising:
- performing a holographic imaging of a flow of a heterogeneous population of cells to enable label-free quantitative imaging of the flow of cells, wherein said performing the holographic imaging comprises at least one of the following:
- (i) performing a digital holographic microscopy and quantitative phase microscopy to measure the quantitative phase profile of the cell being indicative of the optical path delay (OPD) profile of the cell to enable label-free interferometric phase microscopy;
- or
- (ii) obtaining a plurality of off-axis holograms and performing a quantitative phase reconstruction process;
- automatically processing image data of the holographic imaging to identify a certain type of cells during the flow, wherein:
- said automatically processing the image data comprises at least one of the following:
- (a) reconstructing the OPD map for each cell individually;
- or (b) extracting from each OPD 2D and 3D morphological and quantitative features;
- and
- said automatically processing the image data comprises performing classification based on 2D and 3D morphological quantitative features of the cells during the cell flow, by carrying out at least one of the following:
- performing a real-time classification of each cell;
- or performing classification of unlabeled cancer cells in blood to enable label-free imaging and sorting of cancer cells in blood;
- and further comprises automatically classifying primary and metastatic cancer cells;
- and
- automatically sorting the certain type of cells during flow, thereby obtaining a real-time, automatic, label-free holography-activated sorting of the cells.
12 more elements
Dependencies are inferred from the claim text.