A survey of electrokinetically‐driven microfluidics for cancer cells manipulation

Abstract

Cancer is one of the leading causes of annual deaths worldwide, accounting for nearly 10 million deaths each year. Metastasis, the process by which cancer spreads across the patient's body, is the main cause of death in cancer patients. Because the rising trend observed in statistics of new cancer cases and cancer‐related deaths does not allow for an optimistic viewpoint on the future—in relation to this terrible disease—the scientific community has sought methods to enable early detection of cancer and prevent the apparition of metastatic tumors. One such method is known as liquid biopsy, wherein a sample is taken from a bodily fluid and analyzed for the presence of CTCs or other cancer biomarkers (e.g., growth factors). With this objective, interest is growing by year in electrokinetically‐driven microfluidics applied for the concentration, capture, filtration, transportation, and characterization of CTCs. Electrokinetic techniques—electrophoresis, dielectrophoresis, electrorotation, and electrothermal and EOF—have great potential for miniaturization and integration with electronic instrumentation for the development of point‐of‐care devices, which can become a tool for early cancer diagnostics and for the design of personalized therapeutics. In this contribution, we review the state of the art of electrokinetically‐driven microfluidics for cancer cells manipulation.

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

“…Electrokinetic phenomena have also been used for the isolation and detection of EVs [130][131][132][133][134]. Aïzel et al used a radial geometry in a micro-nanofluidic device for the enrichment of viruses and exosomes [135].…”

A review: Dielectrophoresis for characterizing and separating similar cell subpopulations based on bioelectric property changes due to disease progression and therapy assessment

“…Several reviews cover studies focused on dielectrophoresis for characterization and separation of cancer cells from other cells [11,40]. Most notably, dielectrophoresis has been extensively studied for the isolation of rare cancer cells, circulating tumor cells (CTCs), from the blood for early diagnostics [9,10].…”

“…Several reviews cover DEP applications in regard to live/dead cell separations, subcellular/nanoscale characterization [7,8], and even rare cell isolation from heterogeneous samples [9][10][11][12][13][14], spanning over several organisms from cancer to bacteria to proteins. These applications, however, do not exploit the high-sensitivity potential of dielectrophoresis and its ability to detect minute intrinsic differences between similar or related cells for clinical applications.…”

Emerging on‐chip electrokinetic based technologies for purification of circulating cancer biomarkers towards liquid biopsy: A review

“…In addition, on-chip electrokinetics can facilitate the realization of an integrated and automated micro total analysis system (μTAS) [48], in which sample preparation, separation, and detection are performed on a single miniaturized platform. Many excellent articles have been published to review and summarize the on-chip techniques for isolating cells, nucleic acids, exosomes, and proteins [5,16,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63]. For instance, the focuses on microfluidic technologies for isolation and detection of cancer-related biomarkers were comprehensively reviewed in a few articles [5,16,49,52,54]; recent DEP-based technologies and their biological applications were reviewed in [57]; the challenges for next-generation point-of-care molecular diagnostics using the cancer-related biomarkers in blood have been highlighted in [58]; the electrokinetic strategies for exosome isolation were summarized in [59]; the electrokinetically-driven microfluidics for CTC manipulation were reviewed in ref.…”

“…For instance, the focuses on microfluidic technologies for isolation and detection of cancer‐related biomarkers were comprehensively reviewed in a few articles [5,16,49,52,54]; recent DEP‐based technologies and their biological applications were reviewed in [57]; the challenges for next‐generation point‐of‐care molecular diagnostics using the cancer‐related biomarkers in blood have been highlighted in [58]; the electrokinetic strategies for exosome isolation were summarized in [59]; the electrokinetically‐driven microfluidics for CTC manipulation were reviewed in ref. [61]; and the recent innovation in protein separation on microchips by electrophoretic methods was highlighted in [60]. Our review here is distinct from these reviews as we solely focus on the on‐chip electrokinetic‐based isolation and purification techniques for all circulating cancer biomarkers including CTCs, cell‐free nucleic acids ( cf NAs), exosomes and proteins.…”