Exosomes are nano-scale membrane-encapsulated vesicles produced by the majority of cells and have emerged as a rich source of biomarkers for a wide variety of diseases. Although many approaches have been developed for exosome isolation from biofluids, most of them have substantial shortcomings including long processing time, inefficiency, high cost, lack of specificity and/or surface marker-dependency. To address these issues, here we report a novel insulator-based dielectrophoretic (iDEP) device predicated on an array of borosilicate micropipettes to rapidly isolate exosomes from conditioned cell culture media and biofluids, such as plasma, serum, and saliva. The device is capable of exosome isolation from small sample volumes of 200 μL within 20 minutes under a relatively low (10 V cm⁻¹) direct current (DC). This device is easy to fabricate thus, no cleanroom facility and expensive equipment are needed. Therefore, the iDEP device offers a rapid and cost-effective strategy for exosome isolation from biofluids in timely manner while maintaining the yield and purity.

An insulator-based dielectrophoresis (iDEP) is a label-free method that has been extensively utilized for manipulation of nanoparticles, cells, and biomolecules. Here, we present a new iDEP approach that can rapidly trap nanoparticles at the close proximity of a glass nanopipette’s tip by applying 10 V/cm direct current (DC) across the pipette’s length. The trapping mechanism was systemically studied using both numerical modeling and experimental observations. The results showed that the particle trapping was determined to be controlled by three dominant electrokinetic forces including dielectrophoretic, electrophoretic and electroosmotic force. Furthermore, the effect of the ionic strength, the pipette’s geometry, and the applied electric field on the entrapment efficiency was investigated. To show the application of our device in biomedical sciences, we demonstrated the successful entrapment of fluorescently tagged liposomes and unlabeled plasma-driven exosomes from the PBS solution. Also, to illustrate the selective entrapment capability of our device, 100 nm liposomes were extracted from the PBS solution containing 500 nm polystyrene particles at the tip of the pipette as the voltage polarity was reversed.

Cancer is primarily a disease of dysregulation – both at the genetic level and at the tissue organization level. One way that tissue organization is dysregulated is by changes in the bioelectric regulation of cell signaling pathways. At the basis of bioelectricity lies the cellular membrane potential or V_mem, an intrinsic property associated with any cell. The bioelectric state of cancer cells is different from that of healthy cells, causing a disruption in the cellular signaling pathways. This disruption or dysregulation affects all three processes of carcinogenesis – initiation, promotion, and progression. Another mechanism that facilitates the homeostasis of cell signaling pathways is the production of extracellular vesicles (EVs) by cells. EVs also play a role in carcinogenesis by mediating cellular communication within the tumor microenvironment (TME). Furthermore, the production and release of EVs is altered in cancer. To this end, the change in cell electrical state and in EV production are responsible for the bioelectric dysregulation which occurs during cancer. This paper reviews the bioelectric dysregulation associated with carcinogenesis, including the TME and metastasis. We also look at the major ion channels associated with cancer and current technologies and tools used to detect and manipulate bioelectric properties of cells.

Isolation of circulating biomarkers using microfluidic devices for cancer diagnosis.