Characterization of single nuclei in an electro-optical cytometer for metaphase detection

Analysis of metaphase chromosomes is crucial for the diagnosis of genetic disorders and some forms of cancer. From international guidelines, analysing a minimum of 20 metaphases is deemed essential for diagnosing a normal karyotype. However, this is a difficult and time-consuming process, due to the low fraction of metaphases in bone marrow and blood cell samples. Therefore, an automated and high-throughput system which enriches and collects metaphases could be a valuable aid to clinicians. For this purpose, a new microfluidic method to identify potential metaphases is proposed, using impedance signatures of individual flowing nuclei and synchronized optical images. Specifically, impedance signals are used to identify nucleus-containing frames which are then processed to extract the contour of each nucleus. Feature extraction is then performed, and both unsupervised hierarchical clustering and supervised support vector machine (SVM) algorithms are implemented to identify potential metaphases.