Strategies for automated fetal cell screening

Studies to date have demonstrated fetal sex determination and aneuploidy detection from maternal blood, but a clinical screening technique has not yet emerged. A key limiting factor is the small number of fetal cells, which makes detection specificity and reliability critical. Visual inspection of unsorted or sorted fetal cells is laborious, and cells can be easily missed. Moreover, it is impractical to examine manually all the separated cells. It is highly likely that automation may increase the number of cells inspected, resulting in higher detection sensitivities. Flow and image cytometry are two feasible approaches for automated detection of cells. This review details computerized microscopy (image cytometry) techniques for the automatic detection of fetal cells. Microscopy-based approaches used to identify fetal origin include: (i) immunocytochemical identification of fetal haemoglobin-specific cells (light or fluorescence microscopy); (ii) identification of sex chromosomes and/or aneuploidy using fluorescence in-situ hybridization; and (iii) morphological identification of nucleated red blood cells using light microscopy. The relevant instrumentation, including motorized stages and filters, cameras and digitizer boards are discussed, and software algorithms, including image enhancement, autofocusing, object detection and relocation, and features for operator review and data analysis, are outlined.