Fig. 1: The MATCH platform.

a Schematic of the MATCH platform. The technology leverages multi-gradient matching to engineer 3D magnetic response for direct and programmable biomolecular detection in native biofluids. It features an array of responsive DNA hydrogel pillars suspended above a GMR sensor; each pillar encapsulates gradient-distributed MNPs which are released upon target incubation. To match the sensor’s intrinsic responsiveness gradient (i.e., that decays rapidly perpendicular to the sensor surface), the MNP and analyte gradients are enriched near the tips of the hydrogel pillars. Target analyte can focally activate the hydrogel pillars to preferentially release sensor-proximal MNPs, generating a magnetic response that spatially complements the sensor’s intrinsic detection capability. b Target-induced MNP release from the hydrogel pillars. The MNP-embedded hydrogel pillars comprise polymer backbones and DNA crosslinkers. Target analyte hybridizes with one of the DNA crosslinkers and displaces the other, forming an endonuclease (Nb.BssSI) cut site. Enzymatic cleavage disrupts the hydrogel network and releases the encapsulated MNPs, causing a change in the GMR magnetic signal. c Scanning electron micrograph of the MATCH hydrogel pillar array. This experiment was repeated thrice independently with similar results. d MNP and analyte gradients. Confocal fluorescence images at different heights of the hydrogel pillars (h) encapsulating ATTO590-conjugated MNPs (top) or incubated with FAM-labeled analyte (bottom) confirmed the establishment of the MNP and analyte gradients, respectively. Scale bar, 100 μm. This experiment was repeated thrice independently with similar results. e Schematic of the MATCH microfluidic device. To complement the MATCH assay workflow, the device integrates the following functional modules: (1) molecular translation module for target recognition and translator release; (2) mixing module, an array of 45° parallelogram barriers to improve local mixing; (3) signal transduction module with MNP-loaded hydrogel pillars for gradient-matched detection of the released translators. The inset shows optical micrographs of the GMR sensor before (top) and after (bottom) the patterning of the hydrogel pillars (red circle). Inset scale bar, 100 μm. f MATCH platform for cancer diagnostics. The technology combines molecular translation and gradient-matched transduction for direct, sensitive detection of circulating nucleic acid and protein biomarkers in native plasma lysates, and effectively distinguishes cancer patients from healthy individuals.