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Ghost cytometry

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Science  15 Jun 2018:
Vol. 360, Issue 6394, pp. 1246-1251
DOI: 10.1126/science.aan0096

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Seeing ghosts

In fluorescence-activated cell sorting, characteristic target features are labeled with a specific fluorophore, and cells displaying different fluorophores are sorted. Ota et al. describe a technique called ghost cytometry that allows cell sorting based on the morphology of the cytoplasm, labeled with a single-color fluorophore. The motion of cells relative to a patterned optical structure provides spatial information that is compressed into temporal signals, which are sequentially measured by a single-pixel detector. Images can be reconstructed from this spatial and temporal information, but this is computationally costly. Instead, using machine learning, cells are classified directly from the compressed signals, without reconstructing an image. The method was able to separate morphologically similar cell types in an ultrahigh-speed fluorescence imaging–activated cell sorter.

Science, this issue p. 1246

Abstract

Ghost imaging is a technique used to produce an object’s image without using a spatially resolving detector. Here we develop a technique we term “ghost cytometry,” an image-free ultrafast fluorescence “imaging” cytometry based on a single-pixel detector. Spatial information obtained from the motion of cells relative to a static randomly patterned optical structure is compressively converted into signals that arrive sequentially at a single-pixel detector. Combinatorial use of the temporal waveform with the intensity distribution of the random pattern allows us to computationally reconstruct cell morphology. More importantly, we show that applying machine-learning methods directly on the compressed waveforms without image reconstruction enables efficient image-free morphology-based cytometry. Despite a compact and inexpensive instrumentation, image-free ghost cytometry achieves accurate and high-throughput cell classification and selective sorting on the basis of cell morphology without a specific biomarker, both of which have been challenging to accomplish using conventional flow cytometers.

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