RESUMEN
Cancer diagnosis has recently been at the forefront of recent medical research, with ongoing efforts to develop devices and technologies for detecting cancer in patients. One promising approach for cancer diagnosis is the detection of Circulating Tumor Cells (CTCs) in blood samples. Separating these rare cells from the diverse background of blood cells and analyzing them can provide valuable insights into the disease's stage and lethality. Here we present the design and fabrication of a centrifugal microfluidic platform on a polymeric disk that utilizes centrifugal forces for cell isolation. The separation units exploit both active and passive methods. In other words, in addition to introducing novel geometry for channels, an external magnetic field is also employed to separate the target cells from the background cells. In order for the external field to function, the CTCs must first be labeled with antibody-conjugated nanoparticles; the separation process should be then performed. Before the experimental tests, a numerical study was done to determine the optimum parameters; the angular velocity and magnetization investigations showed that 2000 rpm and 868,000 (kA/m) are the optimum conditions for the designed device to reach the efficiency of 100% for both White Blood Cells (WBCs) and CTCs. These results indicate that the passive region of the channels primarily contributes to the focusing of the target cells, and showed that the focusing effect is more pronounced in the expansion-contraction geometry compared to the zigzag geometry. Additionally, the results proved that curved channel geometries performed better than straight ones in terms of separation efficiency. However, if the separation relies solely on channel geometry, the majority of cells would be directed towards the non-target chamber, leading to suboptimal results. This is due to the direction of the forces acting on the cells. However, including an external magnetic field improves the direction of the net force and enhances the separation efficiency. Finally, the numerical and experimental results of the study were compared, and the curved expansion-contraction channel is introduced as the best geometry having 100% and â¼92% CTC separation efficiency, respectively.
Asunto(s)
Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Humanos , Microfluídica/métodos , Células Neoplásicas Circulantes/patología , Separación Celular , Línea Celular Tumoral , Fenómenos MagnéticosRESUMEN
Being the second cause of mortality across the globe, there is now a persistent effort to establish new cancer medication and therapies. Any accomplishment in treating cancers entails the existence of accurate identification systems empowering the early diagnosis. Recent studies indicate CTCs’ potential in cancer prognosis as well as therapy monitoring. The chief shortcoming with CTCs is that they are exceedingly rare cells in their clinically relevant concentration. Here, we simulated a microfluidic construct devised for immunomagnetic separation of the particles of interest from the background cells. This separation unit is integrated with a mixer subunit. The mixer is envisioned for mixing the CTC enriched stream with lysis buffer to extract the biological material of the cell. Some modification was proposed on mixing geometry improving the efficacy of the functional unit. A valuation of engaged forces was made and some forces were neglected due to their order of magnitude. The position of the magnet was also optimized by doing parametric study. For the mixer unit, the effect of applied voltage and frequency on mixing index was studied to find the optimal voltage and frequency which provides better mixing. Above-mentioned studies were done on isolated units and the effect of each functional unit on the other is not studied. As the final step, an integrated microfluidic platform composed of both functional subunits was simulated simultaneously. To ensure the independence of results from the grid, grid studies were also performed. The studies carried out on the construct reveal its potential for diagnostic application.