Two-photon polymerization based microfluidic biochip incorporating a herringbone microchannel and deterministic lateral displacement design for efficient capture of circulating tumor cells

Circulating tumor cells (CTCs) are cells that become detached from a primary tumor and enter the vascular or lymphatic system. These cells contain nearly the entire genetic information of the primary tumor. Enrichment and detection of CTCs play a crucial role in prognostications and risk assessments of tumor metastasis and recurrence, evaluation of efficacy and potential medications for precision tumor therapy, and detection of dynamic biomarkers during tumor treatment. Current methods of CTC capture often face the challenge of balancing capture rate and purity. To address these issues, we propose a microfluidic biochip based on the principle of immunoaffinity, which incorporates a herringbone microchannel and deterministic lateral displacement (DLD) technology for the capture of CTCs. By manipulating the internal structural design of the microfluidic chip, we optimized the flow field within the chip, thereby enhancing the contact frequency between cells and aptamers and ultimately improving the capture rate. The proposed chip demonstrated a capture efficiency of approximately 91.87% for human breast cancer cells (MCF7), with a release rate of 77.5%. The relative activity of the released cells was approximately 94.08%. Notably, the specificity of the aptamers toward tumor cell surface antigens enables high-purity capture. Additionally, the use of DNA enzymes to digest aptamers facilitates the release of high-activity CTCs, offering a method to simultaneously achieve a high capture rate, purity, and activity enrichment.