Glucometer Readout for Portable Detection of Heterogeneous Circulating Tumor Cells in Lung Cancer Captured on a Dual Aptamer Functionalized Wrinkled Cellulose Hydrogel Interface

The rarity of circulating tumor cells (CTCs) poses a great challenge to their clinical application as reliable "liquid biopsy" markers for cancer diagnosis. Meanwhile, the epithelial-mesenchymal transition (EMT) led to a reduced efficiency in capturing cells with lost or downregulated epithelial cell adhesion molecule (EpCAM) expressions. In this study, we proposed an integrated, highly efficient strategy for heterogeneous CTC capture and portable detection from the blood of non-small-cell lung cancer (NSCLC) patients. First, the cellulose wrinkled hydrogel with excellent biocompatibility and high specific area was employed as the biointerface to capture heterogeneous CTCs with an improved capture efficiency in virtue of dual targeting against epithelial and mesenchymal ones. Meanwhile, the strategy of glucometer readout was introduced for the quantification of captured CTCs on the same hydrogel interface by a detection probe, Au-G-MSN-Apt, which was fabricated via entrapping glucose into the amino group functionalized mesoporous silica nanoparticle (MSN) framework sealed by l-cysteine modified gold nanoparticles (AuNPs) and then linked with dual aptamers of EpCAM and Vimentin. The number of captured CTCs on the hydrogel could be reflected according to the portable glucose meter (PGM) readings. Moreover, it was found that the captured cells maintained a higher viability on the hydrogel and could be in situ recultured without releasing from the substrate. Finally, this integrated strategy was successfully applied to inspect the correlations between the number of heterogeneous CTCs in the blood of NSCLC patients with disease stage and whether there was distant metastasis.