Rapid preparation and single-cell analysis of concentrated blood smears using a high-throughput blood cell separator and a microfabricated grid film

•A new approach for rapid preparation and single-cell analysis of concentrated blood smears.•Parametric studies for optimization of deterministic migration-based white blood cell separation.•Demonstration of the virtual overlay of a microfabricated grid film onto a blood smear.•The approach was successfully applied for cytological examination of concentrated blood smears and detection of a rare white cell subpopulation.

Cytological examination of peripheral white blood cells inhomogeneously distributed on a blood smear is currently limited by the low abundance and random sampling of the target cells. To address the challenges, we present a new approach to prepare and analyze concentrated blood smears by rapidly enriching white blood cells up to 32-fold with 92% recovery on average at a high throughput (1 mL/min) using a deterministic migration-based separator and by systematically analyzing a large number of the cells distributed over a blood slide using a microfabricated grid film. We anticipate that our approach will improve the clinical utility of blood smear tests, while offering the capability to detect rare cell populations.