Portable duplex digital PCR for on-site detection of IDH mutations in gliomas

초록

Accurate identification of critical genetic markers in brain tumors, such as isocitrate dehydrogenase (IDH) mutations, is vital for predicting overall survival, which can reach 11.4 years for IDH-mutant gliomas compared to 14.6 months for IDH-wildtype glioblastoma (GBM). However, existing diagnostic methods, including immunohistochemistry and next-generation sequencing, are time-consuming and difficult to implement in post-surgical contexts. Here, we present a proof-of-concept for a portable, duplex droplet-based digital PCR (ddPCR) system that integrates thermocycling, microfluidic control, and multi-fluorescence detection within a compact design, enabling rapid and accurate analysis of rare mutations. In contrast to conventional ddPCR platforms, which are often bulky, complex, and unsuitable for point-of-care use, our system features an automated, user-friendly workflow that reduces operator variability while maintaining high sensitivity and specificity. Using patient-derived glioma samples, we demonstrated that the system successfully distinguished IDH-mutant from IDH-wildtype tumors, achieving 92 % sensitivity and 100 % specificity. Moreover, comparison with a commercial ddPCR platform showed strong concordance, validating its analytical accuracy and clinical utility. This system offers a promising advancement in molecular diagnostics, providing a field-deployable solution for accurate mutation detection, personalized treatment selection, and improved prognostic evaluation.

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