Purpose: Study of effective isolation of rare cells using specially designed microfluidic filter. Design: A novel microfluidic filter chip is proposed to enhance the isolation efficiency on rare cells, and has been successfully tested with micro beads and A549 cell lines using our unique designs of micro-posts. While most of the other filtration techniques have serious issues of channel clogging and prolonged processing, we have successfully accomplished outstanding improvements from such problems by utilizing inertial displacement through curved structures, built-in bypassing routes, and dedicated trapping zones. A solution containing polystyrene micro beads of 9.9 μm in diameter was successfully separated at the isolation efficiency of 96% with a high flow rate of 1ml/min. Additional experiments were also carried out, with A549 cell-lines in a PBS solution to see the filtration feasibility on bio-particles. Our device may offer an effective and reliable label free separation technique without channel blockage issues. By far, we have studied two design configurations called Model I and Model II. (Model II is an improved version of Model I). Results: Capture efficiency of 96% was recorded from Model II for microbeads at the flowrate of 1ml/min. The capture efficiency of 85% was marked from Model I for microbeads at the flowrate of 1 ml/min. The relationship between the flowrate and capture efficiency has also been studied as shown in Table.1 Conclusion: Our studies demonstrate the excellence of our microfluidic devices with a capture efficiency of 96% and exhibits potential capabilities of isolating circulating tumor cells from peripheral blood of cancer patients. Table 1: Flow rate vs Filtering efficiency of microbeads and A549 cells Flow rate (ml/min)Model - I Filtering efficiency % (Standard Error Mean)Model II Filtering efficiency % (Standard Error Mean)MicrobeadsA549 cellsMicro beadsA549 cells185 (±4.5%)78 (±4.0%)96 (±3.4%)92 (±4.0%)1.580 (±4.0%)71 (±3.5%)90 (±3.1%)85 (±3.4%)273 (±3.5%)65 (±3.1%)84 (±2.8%)80 (±3.0%)2.556 (±2.6%)48 (±2.5%)80 (±2.3%)73 (±2.2%)345 (±2.2%)38 (±1.8%)70 (±2.0%)65 (±1.5%) Citation Format: Nanda Kasani, Manjunath Yeriswamy, Guangfu Li, Jussuf Kaifi, Jae W Kwon. Rare cell isolation by enhanced microfluidic filter using wing-shaped micro posts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3319.
Microfluidics have been applied to filtration of rare tumor cells from the blood as liquid biopsies. Processing is highly limited by low flow rates and device clogging due to a single function of fluidic paths. A novel method using multifunctional hybrid functional microposts was developed. A swift by-passing route for non-tumor cells was integrated to prevent very common clogging problems. Performance was characterized using microbeads (10 µm) and human cancer cells that were spiked in human blood. Design-I showed a capture efficiency of 96% for microbeads and 87% for cancer cells at 1 ml/min flow rate. An improved Design-II presented a higher capture efficiency of 100% for microbeads and 96% for cancer cells. Our method of utilizing various microfluidic functions of separation, bypass and capture has successfully guaranteed highly efficient separation of rare cells from biological fluids.
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