Multifunctional Gelatin Nanoparticle Integrated Microchip for Enhanced Capture, Release, and Analysis of Circulating Tumor Cells

Detection of rare circulating tumor cells (CTCs) from patients has an important effect on clinical cancer diagnosis and prognosis. Here, an integrated microfluidic chip for efficient isolation and downstream analysis of CTCs is developed. This new designed platform, gelatin nanoparticle (GNP) integrated microchip, combines a series of curved herringbone structures, which generate enhanced interactions between CTCs and the immunomodified channel surface, with multifunctional GNP based nanostructured surface, which not only provide more binding sites for antibodies and targets and avoid nonspecific absorption of blood cells due to its electronegative surface charge, but also enable viable cell release under a mild enzymatic treatment. The chip allows cell isolation with ≈85% capture yield and ≈90% release efficiency using spiked cell samples. Results demonstrate that the released cancer cells maintain good viability and proliferation ability. Furthermore, the microchip is successfully applied to capture noninvasive release and genetically analyze CTCs from clinical cancer patients. The proposed platform may provide a potential in clinics. A new microfluidic chip consisting of modified herringbone structures incorporated with continuously curved channels and a multifunctional nanointerface created by gelatin nanoparticles within the microchip is fabricated. Circulating tumor cells are efficiently recovered from cancer patients, and downstream analysis of gene mutation is further achieved. The proposed platform demonstrates a great potential for future clinical applications.