Detection of 'rare event' fetal erythroblasts in maternal blood using automated microscopy

This paper describes the use of automated microscopy to detect fetal erythroblasts in maternal blood. The technology is based on the following approach: (1) the use of centrifugal cytology for the preparation of monolayers; (2) simultaneous staining of fetal hemoglobin (immunoalkaline phosphatase) and chromosome sequences (FISH); (3) multi-mode microscopy to detect rare events; (4) visual evaluation of image memories containing detected objects. Model systems show that fetal cells in frequencies as low as 1 in a million cells can be detected easily (manually or by automated microscopy). Algorithms for automated cell selection were developed for a test set of 6 patients. Optimization of hardware and software routines will make analysis of several million cells in approximately 1 h feasible.