Rapid and precise tumor cell separation using the combination of size-dependent inertial and size-independent magnetic methods

Circulating tumor cells (CTCs) play a significant role in cancer diagnosis and treatment monitoring. One of the major challenges in isolating and detecting rare CTCs from blood is that white blood cells (WBCs) have a size overlap with the target CTCs. To address this issue, we constructed a three-stage i-Mag device integrated with passive inertial microfluidics and active magnetophoresis, enabling rapid and precise separation of tumor cells from blood. The first-stage spiral inertial sorter was applied to rapidly remove small-sized red blood cells (RBCs), and then the second-stage serpentine inertial focuser and the third-stage magnetic sorter were used for removing the magnetically labeled WBCs size-independently, to significantly purify the captured tumor cells. Then, the separation performance of our i-Mag device was explored. The results indicated rapid and precise separation of breast cancer cells from diluted whole blood at a high separation efficiency of 93.84% and at a high purity of 51.47%. The purity of the collected tumor cells could be further improved to 93.60% when the blood dilution ratio was increased. We also successfully applied our i-Mag device for the isolation and detection of trace tumor cells. Our i-Mag device has numerous advantages, such as enabling high-throughput processing and high-precision separation, requiring easy manufacturing at a low cost, and providing tumor antigen-independent operation. We believe that the i-Mag device has great potential to act as a precise tool for separating various bioparticles.