Utilizing framework nucleic acids for integrated nano-micro interface system in circulating tumor cells (CTCs) detection, cultivation, and single-cell analysis

Abstract

The detection and cultivation of circulating tumor cells (CTCs) play a crucial role in monitoring tumor recurrence, metastasis, early disease diagnosis, and assessing the effectiveness of drug treatments. This study specifically focused on investigating human breast cancer cells MCF-7 by utilizing framework nucleic acids (FNAs) as bio-probe scaffold in conjunction with fishbone structures and three-dimensional (3D) microcavity structures within microchannels. These components collectively formed an integrated nano-micro interface system designed for a comprehensive examination of CTC detection and cell culture. The study involved the assessment and comparison of rigid 3D FNAs with distinct side lengths of 7, 13, and 26 bases. This approach not only allowed for precise regulation of the DNA biosensor interface through the manipulation of probe spacing, facilitating optimal probe-cell interactions within the microfluidic channel. Consequently, this approach significantly enhances capture efficiency and lowers the CTC detection limit to 5 cells/mL. Moreover, this research successfully observed cell proliferation and individual cell biological behavior within the 3D microcavity structure. The findings indicated that the overall cell population's proliferation was like that in static culture conditions. Although the proliferation cycle of individual cells was notably extended, cell mobility within the microcavity demonstrated their robust biological activity. These significant outcomes not only offer a practical approach for early tumor detection but also provide a valuable pathway for comprehending mechanisms of tumor development and advancement and guiding personalized treatment strategies effectively.