Tunable cell separation using a thermo-responsive deterministic lateral displacement device

Abstract

Tunability in isolating target cells of varying sizes from complex heterogeneous samples is essential for biomedical research and diagnostics. However, conventional deterministic lateral displacement (DLD) systems lack flexibility due to their fixed critical diameters (D_c). Here, we present a thermo-responsive DLD micropillar array that enables tunable cell separation by dynamically modulating D_c through temperature control. Our device integrates poly(N-isopropylacrylamide) (PNIPAM) hydrogel micropillars within a PDMS-silicon microfluidic chip mounted on a Peltier element, enabling precise D_c adjustments from 0.8 to 29.0 μm within a temperature range of 20–40 °C. Transient and steady-state simulations confirmed that the silicon substrate enhances thermal performance, ensuring rapid and uniform temperature regulation. Using blood samples containing human breast adenocarcinoma cells (MCF-7), we demonstrated three separation modes: (i) major separation at 25 °C, isolating MCF-7 cells (average size: 17.6 μm) with 100% purity; (ii) selective separation at 26 °C, targeting larger MCF-7 subpopulations (average size: 18.7 μm); (iii) minimal separation at 37 °C. All processes preserved cell viability. These findings highlight the potential of our thermo-responsive DLD platform for precise, temperature-controlled cell selection, offering broad applications in biomedical research and diagnostics.