Free-floating tumor cells in the bloodstream of cancer patients, or circulating tumor cells (CTCs), are an often studied, important cellular subset used to identify metastatic potential. While many exciting technologies are being developed to isolate these rare cell populations, nearly all studies with CTCs are conducted in culture conditions that fail to mimic the free-floating conditions during metastasis, thus hindering investigation of the properties of CTCs in their native environment. For example, when breast cancer cells are free-floating after extracellular matrix detachment, these cells exhibit dynamic tubulin-based extensions known as microtentacles (McTNs). McTNs contribute to cellular aggregation and reattachment, thus increasing metastatic efficiency when present. Here, we employed a polyelectrolyte multilayer (PEM) system deposited on a microfluidic device to fabricate a cytophobic surface which recapitulates the native environment in the bloodstream, allowing for cells to maintain their free-floating properties. To improve upon the design, a lipid moiety was added to tether cells to the microfluidic device through interacts between the lipid and cell membranes (Fig. 1A). Since coatings were optically clear, these surfaces allowed for real-time, high-resolution imaging and enumeration of McTNs. We found that lipid tethering could eliminate confounding imaging effects such as cell drifting over time and contribute to diagnosis of metastatic potential (Fig. 1B). After tethering, real-time analysis of McTN response to various chemotherapeutic treatments was performed (Fig. 1C) and quantification McTN numbers and dynamics was determined, allowing for screening of potential drug candidates which could inform patient treatment decisions. Ongoing investigations show that CTCs from patient derived xenografts can also be tethered, creating opportunities to further understand McTNs and other biological characterizations of CTCs which may ultimately be used in conjunction with physicians and pathologists recommendations to improve patient diagnosis and treatment.

Immobilization of circulating tumor cells via polyelectrolyte multilayers allows for free-floating cell visualization and drug screening

253rd National Meeting (2017)

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