Scalable Multilayer Cell Collector to Capture Circulating Tumor Cells with an Unlimited Volume Capacity

Circulating tumor cells (CTCs) have been suggested as the precursors of metastatic cancer. CTC-based characterization has thus been used to monitor tumor status before the onset of metastasis and has shown to be an independent factor. The low abundance of CTCs, however, makes it challenging to employ CTC as a clinical routine, thus making it impossible to address tumor heterogeneity. Here, we present a cell collection prototype for an efficient capture of CTCs from a large volume of body fluids such as blood. An antibody-PEG modified multilayer matrix column is engineered and connected to an apheresis-based circulation system. This setup allows us to capture CTCs repetitively from an unlimited sample volume through the circulation system, thereby increasing the capture count. Compared to conventional CTC capturing devices where the sample handling is generally limited to 1-10 mL, our collector is able to handle a wide range of fluidic sample (40-2000 mL) at a high flow rate (400 mL/min). By processing 90 min in circulation, we obtained an average capture efficiency of at least 75% for the colorectal cancer cell line HCT116 spiked in either 40-200 mL of buffer solution or 40 mL of a whole blood sample. This result highlights a possibility to construct personalized CTC libraries through high-throughput CTC collection for the study of tumor heterogeneity in precision medicine.