Ultrathin silicon nitride membrane with slit-shaped pores for high-performance separation of circulating tumor cells

In this study, we developed an ultrathin filtering membrane with slit-shaped pores which can achieve circulating tumor cell (CTC) separation from whole blood with high performance (high capture efficiency, high white blood cell (WBC) depletion, and high viability). The silicon nitride (Si₃N₄) filtering membrane was fabricated via the standard microfabrication technology, which can be easily scaled up to mass-production. 6 μm was determined as the optimum width of the filtering pores to better separate CTCs in whole blood, which can reach a high capture efficiency of ∼96%. Meanwhile, the filtering membrane with a high porosity of 34% demonstrated high WBC depletion (∼99.99%). Furthermore, the ultrathin (thickness: 200 nm) Si₃N₄ membrane facilitated the capture of CTCs with high viability (∼90%). Finally, the microfluidic chip was successfully applied to separate CTCs in whole blood samples from cancer patients and used for molecular examination. These results indicate that this microfluidic chip facilitates the clinical application of CTC-based liquid biopsy technology.