Circulating tumor cells isolation using microfilters on a microchip

Hajar Moghadas,1,* Naeim jalali,2 Mahdi moghimi,3 Mohammad seyedjalali,4

1. Department of Gas and Petroleum, Yasouj University, Gachsaran 75918-74831, Iran
2. Department of Mechanical Engineering, Iran University of Science and Technology (IUST), Tehran, Iran
3. Department of Mechanical Engineering, Iran University of Science and Technology (IUST), Tehran, Iran
4. Mizan Microfabrication Technologies Co., Tehran, Iran

Abstract


Introduction

One of the strange characteristics of the cancer tissue is that their cells are very loose. the cancer cells are able to separate from the original tumor and circulate through the blood. in this situation, they are called circulating tumor cells (ctcs) [1]. isolation and detection of the ctcs from the bloodstream not only are singe of the metastasis but also provide valuable information about the cancer diagnosis and treatment [2]. microfluidic devices as a powerful technology have been used greatly for isolating ctcs using different methods such as immunomagnetic, dielectrophoresis, hydrodynamic and size-based filtration methods [3]. the size-based filtration methods applied the physical differences of the particles to separate and isolate them. in these simple methods, there is no need to use any chemical or magnetic agents. here we have produced a microchip to capture ctcs using microfiltration mechanism. the capture efficiency of the microchip has been evaluated by spherical polystyrene particles with an average diameter of 16 µm. these particles have been used as a model of the ctcs that generally are between of 7 to 30 µm.

Methods

The microchip has been fabricated using soft lithography technology with pdms (polydimethylsiloxane). it has been consisting of a main microchannel in which several diamond micropillars have been situated in four stages. the height of the microchannel is 40 µm and the distances between micropillars are 20, 15, 10 and 5 µm in stage 1, stage 2, stage 3 and stage 4, respectively. while the particles have been passed through the microchannel they will be trapped in the free spaces between the micropillars based on their sizes. the particles have been suspended in the distilled water. then the suspension has been injected from into the microchip using a syringe pump at a flow rate of 10 µl/min. to provide air bubbles trapping between the micropillars first distilled water has been injected into the microchannel at a flow rate of 2 µl/min for 5 minutes.

Results

The suspended particles have been inserted into the microchip at a flow rate of 10 µl/min. as it has been shown in fig. all the particle passes through the first stage with 20 µm free space between the micropillars. however, all of them have been trapped in the second stage with 15 µm free space. none of the particles was able to escape the second stage as their diameter are 16 µm which is greater than the free space in the second stage that is 15 µm.

Conclusion

These data indicate that the capture efficiency of this microchip is 100 percent for the particles with an average diameter greater than 15 µm. respect to the fact that ctcs are greater than 5 µm, therefore, it is predicted that our microchip is able to capture them. as the future work, the capture efficiency of the microchip will be evaluated by cancer cell lines with different diameter suspended in the culture media as a more realistic model for ctcs.

Keywords

Circulating tumor cells, cancer, microfluidic, filtration