Benefiting from superior programmability and good biocompatibility, DNA nanomaterials have received considerable attention with promising prospects in biological detection applications. However, their poor stability and operability severely impede further development of the applications of DNA nanomaterials. Here, a thermally stable DNA nanomesh structure is integrated into a microfluidic chip. The specificity of the nucleic acid microfluidic capture device could reach the single-base mismatch level while capturing the ssDNA sample. The microfluidic chip provides a closed environment for the DNA nanomesh, giving the device excellent storage stability. After 6 months of storage at room temperature, the device still has a specific capture function on ssDNA samples with low concentration. The specific nucleic acid microfluidic capture device can be applied to the enrichment of ctDNA in the future and contribute to the early diagnosis of cancer.