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.
Authors
- Beng Ti Ang (ORCID: https://orcid.org/0000-0001-7252-5146)
- Yuan Chen (ORCID: https://orcid.org/0000-0003-0992-0121)
- Carol Tang (ORCID: https://orcid.org/0000-0002-1835-5083)
- Auginia Natalia (ORCID: https://orcid.org/0000-0001-7487-6759)
- Balram Chowbay (ORCID: https://orcid.org/0000-0003-4775-9877)
- Tze Ping Loh (ORCID: https://orcid.org/0000-0002-4272-0001)
- Wan‐Teck Lim (ORCID: https://orcid.org/0000-0002-4655-0206)
- John Kit Chung Tam (ORCID: https://orcid.org/0000-0002-6269-3653)
- Huilin Shao (ORCID: https://orcid.org/0000-0003-4513-1410)
- Noah R. Sundah (ORCID: https://orcid.org/0000-0003-1077-263X)
- Li Zhang (ORCID: https://orcid.org/0000-0003-0068-955X)
- Xingjie Wu (ORCID: https://orcid.org/0000-0002-8768-5633)
- Xuecheng Sun (ORCID: https://orcid.org/0000-0001-7377-8225)
- Chi Yan Wong (ORCID: https://orcid.org/0000-0001-8624-8899)
Institutions
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Singapore Immunology Network (SG)
- Singapore Institute for Clinical Sciences (SG)
- Enable Ireland (IE)
- Duke-NUS Medical School (SG)
- National Neuroscience Institute (SG)
- National Cancer Centre Singapore (SG)
- National University Hospital (SG)
- National University Health System (SG)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1038/s41467-024-52754-z
- Citations
- 13
- Primary Topic
- Advanced MRI Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 5.26
Funders
- National Research Foundation
- National University of Singapore
- National Research Foundation Singapore
- Ministry of Education - Singapore
- Directorate for Biological Sciences
- Medical Research Council
- National Medical Research Council