Validation of automatic scanning of microscope slides in recovering rare cellular events: application for detection of fetal cells in maternal blood

ABSTRACT ObjectiveDetection of rare fetal cells (FCs) in the maternal circulation could be used for non‐invasive prenatal diagnosis. Considering that FCs in maternal blood are present in extremely low frequency, manual scanning is cumbersome, time‐consuming, and unsuitable for clinical applications. As an alternative, we optimized a custom‐made classifier for automatic detection of FCs. MethodsUsing MetaSystems' automated platform, we developed a robust detection algorithm and validated its efficiency on retrieval of rare XY cells in a pure population of XX cells. Slides were scanned for presence of predefined XY cells after fluorescence in situ hybridization (FISH) and primed in situ labeling (PRINS). Retrieval of FCs was also performed on samples from maternal blood. ResultsThe efficiency of detection of rare XY cells was 88% using FISH (117/133) in comparison with 78% (53/68) with PRINS. FC frequencies per 1 mL of maternal blood ranged from 3 to 6 FCs in normal pregnancies versus 13 to 21 FCs in Down syndrome pregnancies. ConclusionAutomatic scanning was more efficient and consistent than manual scanning for detection of rare FCs and required considerably less operator time. Automatic scanning using FISH is more sensitive than that using PRINS. The study validates automatic scanning retrieval of FCs from maternal blood. © 2014 John Wiley & Sons, Ltd. What's already known about this topic? In a previous study, we evaluated the efficiency of manual scanning of microscope slides after optimizing a method of spreading slides with a controlled small number of XY cells in a pure population of thousands of XX cells.What does this study add? In this study, we developed a robust custom‐made detection algorithm for detecting rare cellular events using MetaSystems' automated platform and validated its efficiency on 60 slides with a defined number of XY cells identified by fluorescence in situ hybridization (FISH) and 30 slides with primed in situ labeling (PRINS), in comparison with manual scanning, and on maternal blood samples from normal and aneuploid pregnancies.