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9.3 Microfluidic systems in cancer  235




                  with low conductivity. Also, CTC isolation using the dielectrophoresis technic is
                  reported in recent studies [64].
                     Cancer cell separation using acoustic waves (acoustofluidics) is a new way that
                  has been reported in the past few years. An ultra-high-throughput acoustophorestic
                  microdevice, that was able to remove RBCs from human whole blood with 95% effi-
                  ciency, was described by Adams et al. As well, acoustofluidic technology can be used
                  to separate prostate cancer cells from WBCs in blood. Yang and Soh have utilized
                  acoustofluidics in MCF7 breast cancer to sort of viable cells from nonviable [65,66].
                  Nevertheless, cell separation based on acoustic-wave is still in the early stages of
                  research and needs more development and optimization [59]. Novel progress tech-
                  nologies will able the molecular characterization of CTCs and the definition of bio-
                  markers for therapeutic strategies and knowledge of the process of cancer metastasis.
                  Thus implementing CTC analyses as a liquid biopsy using microfluidic lab-on-a-
                  chip medical devices can give new insights into anticancer drug mechanisms.
                     In recent years, many microfluidic platforms in order to CTC detection and isola-
                  tion based on size were presented. The performance of a microfluidic device which
                  enables to capture LNCaP-C4-2 prostate cancer cells with efficiency more than 95%,
                  in such a way that operates under constant pressure at the inlet for blood samples. It
                  creates a uniform pressure differential across all the microchannels in the array. Opti-
                  mization of rows to achieve a capture of more than 95% demonstrated that trapping
                  chambers with five or six rows of microconstriction is needed. The shape of cancer
                  cells deformed in the constriction channel. The blood flow temporarily decreased
                  because of cancer cell deformation [62].
                     CTC measurement is a cancer screening method with a minimum invasion that
                  is useful for the early staging of cancer patients and in monitoring recurrent or meta-
                  static disease. In order to attain decisive results for CTC detection and enrichment,
                  generally, ∼7.5 mL of blood volume is needed due to rare enumeration of CTCs in
                  the blood (1–100 cells/mL). A limitation of the current CTC enumeration systems
                  approved by the US Food and Drug Administration (FDA) namely CellSearchR and
                  AdnaTestR. According to the result of clinical studies, CTC detection in blood in
                  cases of breast cancer, colorectal cancer, and prostate cancer patients can be done by
                  CellSearch [62].
                     The necessity of having minimal sample preprocessing is ideal for CTC isolation
                  and enrichment that can avoid loss of CTC and it should have high throughput, high
                  efficiency, high sensitivity, high purity, and low cost. Because of considering these
                  criteria and in order to eliminate the limitations associated with surface-marker-
                  based approaches, the microfluidics has been motivated to develop new CTC tech-
                  nologies based on the biophysical properties of CTCs. These rely on the assumption
                  that biophysical attributes such as size, deformability, permittivity, and conductivity
                  of CTCs are different from blood cell properties. Microchips based on size exclu-
                  sion, deformability, and dielectrophoresis have been explored and shown promising
                  results in CTC collection [67,68]. Also, SAWs that are generated by tilted identical
                  IDTs on microfluidic channels were utilized to CTCs collection of whole blood.
                  For CTC enrichment, finding of balance between capture efficiency, throughput, and
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