On-Chip Continuous Blood Cell Subtype Separation by Deterministic Lateral Displacement

Abstract

This paper presents a microfluidic device for continuous human blood cell subtype separation using the deterministic lateral displacement principle. Based on their significant size and shape differences, three major cell types of human whole blood - platelets, red blood cells and white blood cells -were demonstrated to be directly separated using a two-stage separation strategy. Even though all white blood cells are spherical and have diameters within a narrow range (8-20mum), the initial limitation for using this principle to separate white blood cell subtypes was conquered by attaching larger polystyrene microbeads to one of the subtypes to amplify the size differences. Specifically, continuous separation of human CD4+ T helper lymphocytes from other white blood cell subtypes was achieved with high purity and recovery due to the underlying high affinity and high specificity of the antigen-antibody interaction used to attach the microbeads to the lymphocytes. With our novel approach, the pure population of one blood cell subtype can be effectively isolated by exploring the deterministic lateral displacement principle, which has the advantages of the simplicity, high speed and high resolution. Because many cells express unique surface markers, this method can theoretically be applied to separate any target cell type from a heterogeneous mixture for downstream analysis.