Integrated Biodevice for Parallel Magnetic Isolation and Bioelectrocatalytic Detection of Circulating DNA and RNA Biomarkers in Non-Small Cell Lung Cancer Liquid Biopsy.

The holistic detection of druggable circulating DNA and RNA biomarkers in non-small cell lung cancer (NSCLC) can guide the use of effective targeted drug treatment options for cancer patients. Currently, there is no miniaturized biosensor that can integrate the sample-to-outcome workflow to simultaneously interrogate druggable circulating biomarkers in both DNA and RNA forms. Herein, we present InTegrated CompreHensive Analysis of Nucleic Acids BiOsenSor (THANOS), a customized biodevice technology for integrated magnetic isolation, isothermal amplification, and magneto-bioelectrocatalytic cycling readout of druggable NSCLC DNA and RNA biomarkers from plasma within 50 min. THANOS provided excellent analytical specificity and sensitivity (10 copies) of four NSCLC (EGFR-Del E746-A750 DNA, EGFR-T790M DNA, EGFR-L858R DNA and EML4-ALK RNA) circulating biomarkers. We successfully validated THANOS's excellent biosensing performance in contrived plasma samples against a standard laboratory workflow, which typically requires around 120 min. We envisaged that THANOS could advance the biosensor testing of NSCLC liquid biopsy samples by providing comprehensive guidance on druggable circulating DNA and RNA molecular targets. This may enable a broader identification of circulating DNA/RNA plasma biomarkers essential for targeted NSCLC cancer therapy, thus facilitating timely diagnosis and treatment.