(526a) Isolating Cancer Cells From Blood Using Contactless Dielectrophoresis (cDEP)

Cell enrichment is an important process in many medical and biological applications such as early cancer detection. It has been shown that dielectrophoresis (DEP), the motion of a particle due to its polarization in the presence of a non-uniform electric field, is a method for enrichment of cells based on their electrical properties and size. DEP has been used to separate different cell types. A few pertinent examples include the separation of human leukemia cells from red blood cells in an isotonic solution, entrapment of human breast cancer cells from blood, separation of human monocytic cells from peripheral blood mononuclear cells (PMBC), separation of bacteria from blood, and cancer cells from CD34+ hematopoietic stem cells. This technique has also been used to separate neuroblastoma cells from HTB glioma cells, isolate cervical carcinoma cells, isolate K562 human CML cells, separate live yeast cells from dead, and isolate mammalian cells based on their cell-cycle phase. By changing applied voltage and frequency, media and particles conductivity and permittivity, and geometry of microchannel and electrodes, cell enrichment can be changes.

Although DEP has been a very successful technique to manipulate microparticles, it has some drawbacks such as electrolysis (bubble formation), electrode delamination, and sample contamination, because of contact between sample and electrodes. Also, because of irreversible adsorption, target cells stick to electrodes even after turning off the electric field.

We have invented a new technique, known as contactless dielectrophoresis (cDEP), which provides the spatially non-uniform electric field required for DEP cell enrichment without direct contact between the electrodes and the biological sample. In this method, an electric field is created in the sample microchannel using electrodes inserted into two other microchannels, which are filled with conductive solution and are separated from the sample microchannel by a 20 µm insulating barrier. These insulating barriers exhibit a capacitive behavior and therefore an electric field can be produced in the main channel by applying an AC field across them. The absence of contact between electrodes and the sample fluid inside the channel prevents bubble formation and avoids any contaminating effects the electrodes may have on the sample.

Also since in the cDEP technique electrode channels and main channel are fabricated in the same fabrication step and we don’t need to pattern electrodes, the fabrication process is faster and cheaper comparing to conventional DEP techniques.

Moreover, the trade-off between throughput and purity limits conventional methods of cell enrichment, such as flow cytometry, fluorescent-activated cell sorting (FACS), and magnetic-activated cells sorting (MACS). Almost all conventional DEP devices are low throughput, while most of the applications for cell enrichment, such as isolating CTCs, require high throughput devices. For instance in case of CTC detection there are only a few tumor cells in 1 mL of blood sample (among 10⁹ red blood cells). The flow rate in these DEP based microdevices is restricted by the drag force which should be low enough to be comparable to DEP force. In this study, using parallel wide cDEP microdevices, we reached higher throughput cell enrichment, 1 mL/hr, which is more than 50 times higher than previous generation of cDEP devices.