Deformability-based circulating tumor cell separation with conical-shaped microfilters: concept, optimization and design criteria

Abstract

The ability of detecting and separating CTCs can play a key role in early cancer detection and treatment. In recent years, there has been growing interest in using deformability-based CTC separation microfilters due to their simplicity and low cost. Most of previous studies in this area are mainly based on experimental work. Although experimental research provides useful insights in designing CTC separation devices, there is still a lack of design guidelines based on fundamental understandings of the cell separation process in the filers. While experimental efforts face challenges especially microfabrication difficulties, we adopt numerical simulation here to study conical-shaped microfilters using deformability difference between CTCs and blood cells for separation process. We use liquid drop model for modeling a CTC passing through such microfilters. The accuracy of the model in predicting the pressure signature of the system is validated by comparing with previous experiments. Pressure-deformability analysis of the cell going through the channel is then carried out in detail in order to better understand how a CTC behaves throughout the filtration process. Different system design criteria such as system throughput and unclogging of the system are discussed. Specifically, pressure behavior under different system throughput is analyzed. Regarding the unclogging issue, we define pressure ratio as a key parameter representing the ability to overcome clogging in such CTC separation devices and investigate the effect of conical angle on the optimum pressure ratio. Finally, the effect of unclogging applied pressure on the system performance is examined. Our study provides detailed understandings of the cell separation process and its characteristics, which can be used for developing more efficient CTC separation devices.