Study On Double Spiral Microfluidic Chip For Circulating Tumor Cell Sorting

Circulating tumor cells?CTCs?,shed from primary or metastatic tumors,are extremely rare in peripheral blood circulation.The presence of CTCs in peripheral blood provides a new approach for cancer diagnosis and postoperative evaluation.However,due to their extreme rarity(1-100 CTCs per 10⁹ blood cells),it is very challenging to efficiently capture them.The development of microfluidics and lab on a chip technology provides a new approach for CTCs sorting.Using the Using the Micro Electro-mechanical System?MEMS?technology in Si,polymers,glass,quartz substrate to process millimeter and submillimeter channels,reaction and detection chamber,lab on a chip can precisly control fluid and complete the separation,extraction,analysis and other processes of biological experiments.In this study,after learning the knowledge of fluid mechanics,especially the characteristics of the fluid at micro-scale.The flow state of the fluid in the curved channel of a microfluidic chip and the effect of the fluid on the particle were systematically studied by using the computational fluid dynamics?CFD?simulation software.The Dean vortex distribution in the spiral channel was also simulated.the change of the strength with the fluid velocity and the initial radius of the channel was analyzed.At the same time,the motion of the particles in the channel was studied in details.the model was successfully introduced into the CFD software,and the proof of principle of separating the particles by the double spiral microfluidic chip was simulated.Under the guidance of the simulation results,a 5-loop double spiral microfluidic chip was designed.in which a novel second-order separation approach was proposed.At the first stage of the channel,the largest particals in the sample mixture are separated and pumped out from the specific channel;At the second stage,middle-size particles are sorted,leaving from the other outlets;Smallest particles flow from the remained outlet.In this paper,the chip is fabricated by polymer polydimethylsiloxane?PDMS?.The process includes production of Si mold and pouring of PDMS.The PDMS chip is bonded to the glass substrate by the method of oxygen plasma treatment.We used polystyrene?PS?beads,which have similar sizes of cells as an analog to test the cell sorting performance of the designed microfluidic device.The PS beads with different sizes were diluted in PBS buffer,and pumped into the device.The separation of the PS beads was observed by changing the inlet flow rate of the channel.The result shows that with the increasing of inlet flow rate,20?m particles begin to focus.When the flow rate reaches 30ml/h,20?m particles focus in the equilibrium position at the first stage of the channel and flow out from the left outlet.Due to the channel parameters changed,particles other than 20um continue their movement along the second stage of the channel.And then,12?m particles gradually focus in the equilibrium position,and leave from the middle outlet.From beginning to the end,8?m particles has not reached the focus condition,and flow out from the right outlet.This obtained results showed the ability of the double spiral microfluidic chip to separate multiple particles.