(526b) Design, Development, and Analysis of a Multilayer Contactless Dielectrophoresis Device to Separate Cancer Cells From Blood

The use of non-invasive methods to detect and enrich cancer cells independent of their genotype is critical for early diagnostic and treatment purposes. In addition, isolation of these cells could provide a workbench for clinicians to screen drug therapies prior to patient treatment. This would enable oncologists to tailor treatment on a patient specific level and to ensure the most effective treatment is being utilized. Since many symptoms associated with metastatic cancers, can be attributed to multiple diseases, diagnosis of this disease must be accomplished via medical analysis. There are a number of molecular, cytogenic, immunological cytochemical and morphological assays capable of making this diagnosis, however, the small ratio of cancerous to normal cells make these processes challenging.

During progression, tumor cells acquire the capacity to disseminate into blood circulation until they either are detected and eliminated by the immune system or attach to the endothelial cells, extravasate, and grow as secondary tumors (metastasis) at distant sites. These circulating tumor cells (CTCs) could provide early indicators of metastasis. Typically, techniques for detecting these cells require prior knowledge of cell-specific markers and antibodies. The large amount of sample handling required by these techniques may increase the likeliness of cell loss and contamination. Therefore, there is a growing need for marker-independent isolation and purification method to increase yield, sensitivity, precision and reproducibility.

Dielectrophoresis (DEP), the motion of a particle in a non-uniform electric field, has become a robust method for analyzing nano-particles, cells, viruses, and DNA based on their physical and electrical properties. A new technique, contactless Dielectrophoresis (cDEP), isolates cells from contact with the electrodes. This is achieved by using fluid electrodes which are isolated from the sample channel by thin insulating membranes. 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. This technique has demonstrated the ability to isolate THP-1 human leukemia monocytes from a heterogeneous mixture of live and dead cells as well as discriminate between cells of different metastatic potential. Recently, this technique has been improved for operation at frequencies as low as 1 kHz, allowing us to manipulate cells using both positive and negative DEP. This work presents the development, analysis, and evaluation of a three dimensional, multilayer, cDEP device used to separate cancer cells from blood.