Programmed cell death protein-1 (PD-1) checkpoint immunotherapy efficacy remains unpredictable in glioblastoma (GBM) patients due to the genetic heterogeneity and immunosuppressive tumor microenvironments. Here, we report a microfluidics-based, patient-specific ‘GBM-on-a-Chip’ microphysiological system to dissect the heterogeneity of immunosuppressive tumor microenvironments and optimize anti-PD-1 immunotherapy for different GBM subtypes. Our clinical and experimental analyses demonstrated that molecularly distinct GBM subtypes have distinct epigenetic and immune signatures that may lead to different immunosuppressive mechanisms. The real-time analysis in GBM-on-a-Chip showed that mesenchymal GBM niche attracted low number of allogeneic CD154+CD8+ T-cells but abundant CD163+ tumor-associated macrophages (TAMs), and expressed elevated PD-1/PD-L1 immune checkpoints and TGF-β1, IL-10, and CSF-1 cytokines compared to proneural GBM. To enhance PD-1 inhibitor nivolumab efficacy, we co-administered a CSF-1R inhibitor BLZ945 to ablate CD163+ M2-TAMs and strengthened CD154+CD8+ T-cell functionality and GBM apoptosis on-chip. Our ex vivo patient-specific GBM-on-a-Chip provides an avenue for a personalized screening of immunotherapies for GBM patients.

Rapid, accurate, portable and quantitative profiling of metabolic biomarkers is of great importance for disease diagnosis and prognosis. The recent development in the optical and electric biosensors based on the smartphone is promising for profiling of metabolites with advantages of rapid, reliability, accuracy, low-cost and multi-analytes analysis capability. In this review, we introduced the optical biosensing platforms including colorimetric, fluorescent and chemiluminescent sensing, and electrochemical biosensing platforms including wired and wireless communication. Challenges and future perspectives desired for reliable, accurate, cost-effective, and multi-functions smartphone-based biosensing systems were also discussed. We envision that such smartphone-based biosensing platforms will allow daily and comprehensive metabolites monitoring in the future, thus unlocking the potential to transform clinical diagnostics into non-clinical self-testing. We also believed that this progress report will encourage future research to develop advanced, integrated and multi-functional smartphone-based Point-of-Care testing (POCT) biosensors for the monitoring and diagnosis as well as personalized treatments of a spectrum of metabolic-disorder related diseases.