Postoperative evaluation of tumours based on label-free acoustic separation of circulating tumour cells by microstreaming

Abstract

Metastatic tumour recurrence caused by circulating tumour cells (CTCs) after surgery is responsible for more than 90% of tumour-related deaths. A postoperative evaluation system based on the long-term dynamic detection of CTCs helps in guiding the postoperative treatment of tumours in real time and preventing metastases and recurrence of tumours after treatment. In this study, a simple, rapid, and low-cost postoperative evaluation system was established based on the number of CTCs captured by a label-free acoustic separation device from whole blood samples of mice, of which breast tumours were surgically removed, and tumour metastasis was successfully predicted. First, an acoustofluidic device with a custom-designed bottom microcavity array was fabricated to induce highly localised acoustic microstreaming by applying acoustic vibration. Second, experiments of capturing ‘defined’ cells (artificially mixed individual 4T1 cancer cells into normal blood) based on optimal acoustic streaming were performed. The separation device exhibited a high capture efficiency (>96%). Further applications of capturing the ‘true’ CTCs derived from postoperative mice were successfully developed to predict tumour prognosis based on the number of captured CTCs. Finally, the prediction was verified through long-term observation of mice with excised tumours. The acoustofluidic device can efficiently capture CTCs and precisely predict tumour metastasis in a low-cost and non-invasive manner. This will help clinicians monitor patients that underwent surgical resection of tumours over a long period of time and facilitate optimal treatment strategies in a timely manner.