A Novel Edge Effect Detection Method for Real-Time Cellular Analyzer Using Functional Principal Component Analysis

Real-time cellular analyzer (RTCA) has been generally applied to test the cytotoxicity of chemicals. However, several factors impact the experimental quality. A non-negligible factor is the abnormal time-dependent cellular response curves (TCRCs) of the wells located at the edge of the E-plate which is defined as edge effect. In this paper, a novel statistical analysis is proposed to detect the edge effect. First, TCRCs are considered as observations of a random variable in a functional space. Then, functional principal component analysis (FPCA) is adopted to extract the principal component (PC) functions of the TCRCs, and the first and second PCs of these curves are selected to distinguish abnormal TCRCs. The average TCRC of the inner wells with the same culture environment is set as the standard. If the distance between the scoring point of the standard curve and one designated scoring point exceeds the defined threshold, the corresponding TCRC of the designated point should be removed automatically. The experimental results demonstrate the effectiveness of the proposed algorithm. This method can be used as a standard method to resolve general time-dependent series issues.