Acoustic bubble for spheroid trapping, rotation, and culture: a tumor-on-a-chip platform (ABSTRACT platform).

Cancer is the leading cause of death globally, with 90% of deaths being caused by cancer metastasis. Circulating tumor cells (CTCs) play an important role in early diagnosis of cancer metastasis and in monitoring of therapeutic response. Therefore, reliable methods to isolate, collect and culture CTCs are required to obtain information on metastasis status and therapeutic treatment. In this work, we present a CTC-processing system: acoustic bubble for spheroid trapping, rotation, and culture: a tumor-on-a-chip platform (ABSTRACT). The platform consists of a main channel, several parallel sub-microchannels with microcavities and culture chambers. The microcavity is designed to trap a bubble with desired shape at the entrance of the sub-microchannel. Under the acoustic actuation, the trapped bubble oscillates and creates a secondary radiation force to trap and rotate CTCs at a desired location. By controlling the acoustic bubble, CTCs can be continuously trapped from the blood flow, rotated to form a spheroid, and released to the microchamber for culture. We systematically investigated the effects of device geometry, flow parameters, and input voltage on trapping of CTCs to optimize the performance. Additionally, the successful on-chip spheroid culture demonstrates the biocompatibility and the simplicity of this platform. Besides simplifying conventional complex CTC processing procedures, this ABSTRACT platform also shows great potential for downstream analysis of tumor cells, such as monitoring the progression of metastasis and personalized drug testing.