Magnetic augmentation through multi-gradient coupling enables direct and programmable profiling of circulating biomarkers

Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor’s intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in <60 minutes and achieves sensitive detection (down to 10 RNA and 1000 protein copies). We apply the MATCH to measure RNAs and proteins directly in patient plasma, achieving accurate cancer classification. Conventional magnetic biosensing technologies have limited ability to detect magnetic field dimensionality. Here, the authors develop a platform which uses DNA hydrogels to spatially engineer a 3D magnetic response and demonstrate its use in the direct and programmable detection of RNA and protein biomarkers.