A magnetic resonance tuning sensor for the MRI detection of biological targets


Sensors that detect specific molecules of interest in a living organism can be useful tools for studying biological functions and diseases. Here, we provide a protocol for the construction of nanosensors that can noninvasively detect biologically important targets with magnetic resonance imaging (MRI). The key operating principle of these sensors is magnetic resonance tuning (MRET), a distance-dependent phenomenon occurring between a superparamagnetic quencher and a paramagnetic enhancer. The change in distance between the two magnetic components modulates the longitudinal (T1) relaxivity of the enhancer. In this MRET sensor, distance variation is achieved by interactive linkers that undergo binding, cleavage, or folding/unfolding upon their interaction with target molecules. By the modular incorporation of suitable linkers, the MRET sensor can be applied to a wide range of targets. We showcase three examples of MRET sensors for enzymes, nucleic acid sequences, and pH. This protocol comprises three stages: (i) chemical synthesis and surface modification of the quencher, (ii) conjugation with interactive linkers and enhancers, and (iii) MRI sensing of biological targets. The entire procedure takes up to 3 d.

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Fig. 1: Schematic illustration of a magnetic resonance tuning (MRET) sensor.
Fig. 2: Schematic illustration of the experimental workflow.
Fig. 3: The quencher and its magnetic properties.
Fig. 4: Enhancer and its MRI contrast effects.
Fig. 5: Quencher synthesis.
Fig. 6: Surface modification of the quencher with DMSA.
Fig. 7: Purification of an MRET sensor by a MACS column (Step 22A(v) and (vi)).
Fig. 8: Three different types of MRET sensors.


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We thank S. J. Kim. for helpful discussions and support. This work was supported by grants from the Institute for Basic Science (IBS-R026-D1) and the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs (HI08C2149).

Author information




J.C. conceived and designed the project; T.-H.S., S.K., S.P., and J.-s.C. developed protocols for MRET sensor syntheses; P.K.K. contributed methods for MRI measurements; T.-H.S., S.K., J.-s.C., and J.C. wrote the manuscript.

Corresponding author

Correspondence to Jinwoo Cheon.

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The authors declare no competing interests.

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Key references using this protocol

Choi, J.-s. et al. Nat. Mater. 16, 537–542 (2017): https://doi.org/10.1038/nmat4846

Shin, T. H. et al. ACS Nano 8, 3393–3401 (2014): https://doi.org/10.1021/nn405977t

Choi, J.-s. et al. J. Am. Chem. Soc. 132, 11015–11017 (2010): https://doi.org/10.1021/ja104503g

Lee, J.-H. et al. Nat. Med. 13, 95–99 (2007): https://doi.org/10.1038/nm1467

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Shin, TH., Kang, S., Park, S. et al. A magnetic resonance tuning sensor for the MRI detection of biological targets. Nat Protoc 13, 2664–2684 (2018). https://doi.org/10.1038/s41596-018-0057-y

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