Abstract
Circulating tumor cells (CTCs) isolation from a blood sample plays an important role in cancer diagnosis and treatment. Microfluidics offers a great potential for cancer cell separation from the blood. Among the microfluidic-based methods for CTC separation, the inertial method as a passive method and magnetic method as an active method are two efficient well-established methods. Here, we investigated the combination of these two methods to separate CTCs from a blood sample in a single chip. Firstly, numerical simulations were performed to analyze the fluid flow within the proposed channel, and the particle trajectories within the inertial cell separation unit were investigated to determine/predict the particle trajectories within the inertial channel in the presence of fluid dynamic forces. Then, the designed device was fabricated using the soft-lithography technique. Later, the CTCs were conjugated with magnetic nanoparticles and Ep-CAM antibodies to improve the magnetic susceptibility of the cells in the presence of a magnetic field by using neodymium permanent magnets of 0.51 T. A diluted blood sample containing nanoparticle-conjugated CTCs was injected into the device at different flow rates to analyze its performance. It was found that the flow rate of 1000 µL/min resulted in the highest recovery rate and purity of ~95% and ~93% for CTCs, respectively.
Highlights
Circulating tumor cells (CTCs) captured from blood samples have great potential for the diagnosis and treatment of cancer
These techniques are categorized as microfluidic microfilters, deterministic lateral displacement, hydrodynamic filtration, inertial methods as well as methods based on external force fields such as dielectrophoretic (DEP), acoustic, magnetic, and optical separation methods [3,4]
Label-free cell separation methods function based on the inherent cell properties while affinity-based cell separation approaches use “labels” to capture target cells [5]
Summary
Circulating tumor cells (CTCs) captured from blood samples have great potential for the diagnosis and treatment of cancer. Toner et al [27] proposed an integrated microfluidic device called CTC-iChip, which included a DLD separation unit and inertial focusing channel as well as a magnetophoresis-based cell separation module for capturing CTCs from blood cells. Using magnetically labeled CTCs and a permanent magnet in second cell separator stage of the device, the CTCs can be captured by magnetic cell separator with a higher purity compared to the single inertial channel by eliminating WBCs. By using permanent magnets next to a magnetophoretic cell separation section followed by a focusing region, the CTCs that were conjugated with magnetic nanoparticles are separated from remaining blood cells in the presence of the magnetic field. Because a high-throughput serpentine inertial microfluidic was used in the first-stage, our proposed hybrid device does not have clogging issues and has a simple structure compared to the hybrid devices which use the DLD method for blood cell capturing
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