Ultrasenstive SERS biosensor based on Zn from ZnO nanoparticle assisted DNA enzyme amplification for detection of miRNA.

In this work, a simple and sensitive SERS biosensor was proposed for ultrasensitive detecting miRNA 122 based on ZnO nanoparticle amplification strategy and the full utilization of DNA chain. Firstly, ZnO@S1/S2 and CoFeO@S3 complexes can flock together with the assistance of target miRNA. Accompanied with the incremental amount of miRNA, the quantity of ZnO@S1/S2 would increase. Therefore, a significant amplification capability can be obtained by converting ZnO complexes into Zn with the assistance of HCl. In this case, the DNA chain S2 can be obtained by the ZnO dissolving. In addition, through a clever design, the obtained Zn can be further utilized to induce DNA enzyme cycle amplification to cleave S5 into DNA chain which was similar with DNA S2. This step greatly avoided the waste of DNA chains and improved the utilization efficiency of DNA chains. The S2 and abundant S2 analogues can complement with S4 on the Raman sensing interface to imbed lots of Raman probe DOX for obtaining strong Raman signal. By this way, with the increased number of miRNA, the S2 and abundant S2 analogues would increase, so the amount of DOX would increase to produce strong Raman signal to quantitatively detect target miRNA. As a result, this SERS biosensor based on Zn amplification and high utilization efficiency of DNA chain can obtain a low detection limit of 6.82 aM and wide linear range from 10 aM to 10 pM, which shown great potential in the clinical application and medical diagnosis.