Wireless resonant circuits for the minimally invasive sensing of biophysical processes in magnetic resonance imaging


Biological electromagnetic fields arise throughout all tissue depths and types, and correlate with physiological processes and signalling in organs of the body. Most of the methods for monitoring these fields are either highly invasive or spatially coarse. Here, we show that implantable active coil-based transducers that are detectable via magnetic resonance imaging enable the remote sensing of biological fields. These devices consist of inductively coupled resonant circuits that change their properties in response to electrical or photonic cues, thereby modulating the local magnetic resonance imaging signal without the need for onboard power or wired connectivity. We discuss design parameters relevant to the construction of the transducers on millimetre and submillimetre scales, and demonstrate their in vivo functionality for measuring time-resolved bioluminescence in rodent brains. Biophysical sensing via microcircuits that leverage the capabilities of magnetic resonance imaging may enable a wide range of biological and biomedical applications.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: ImpACTs as imaging probes for functional MRI.
Fig. 2: Theoretical performance of ImpACT designs.
Fig. 3: Tuning and imaging performance of an ImpACT prototype.
Fig. 4: ImpACT-mediated detection of bioluminescence in vitro and in vivo.

Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information. All datasets generated for this study are available from the corresponding author on reasonable request.


  1. 1.

    Grosse, P., Cassidy, M. J. & Brown, P. EEG-EMG, MEG-EMG and EMG-EMG frequency analysis: physiological principles and clinical applications. Clin. Neurophysiol. 113, 1523–1531 (2002).

    CAS  Article  Google Scholar 

  2. 2.

    Jasanoff, A. Bloodless FMRI. Trends Neurosci. 30, 603–610 (2007).

    CAS  Article  Google Scholar 

  3. 3.

    Logothetis, N. K. What we can do and what we cannot do with fMRI. Nature 453, 869 (2008).

    CAS  Article  Google Scholar 

  4. 4.

    Bandettini, P. A. What’s new in neuroimaging methods? Ann. NY Acad. Sci. 1156, 260–293 (2009).

    Article  Google Scholar 

  5. 5.

    Regan, D. Human Brain Electrophysiology: Evoked Potentials and Evoked Magnetic Fields in Science and Medicine (Elsevier, New York, 1989).

    Google Scholar 

  6. 6.

    Merletti, R. & Parker, P. A. Electromyography: Physiology, Engineering, and Non-Invasive Applications Vol. 11 (John Wiley & Sons, Hoboken, 2004).

  7. 7.

    Nunez, P. L. & Srinivasan, R. Electric Fields of the Brain: The Neurophysics of EEG (Oxford Univ. Press, New York, 2006).

  8. 8.

    Bénar, C. et al. Quality of EEG in simultaneous EEG-fMRI for epilepsy. Clin. Neurophysiol. 114, 569–580 (2003).

    Article  Google Scholar 

  9. 9.

    Pandarinath, C. et al. Neural population dynamics in human motor cortex during movements in people with ALS. eLife 4, e07436 (2015).

    Article  Google Scholar 

  10. 10.

    Cash, S. S. & Hochberg, L. R. The emergence of single neurons in clinical neurology. Neuron 86, 79–91 (2015).

    CAS  Article  Google Scholar 

  11. 11.

    Wang, J. Amperometric biosensors for clinical and therapeutic drug monitoring: a review. J. Pharm. Biomed. Anal. 19, 47–53 (1999).

    Article  Google Scholar 

  12. 12.

    Wang, J. Electrochemical biosensors: towards point-of-care cancer diagnostics. Biosens. Bioelectron. 21, 1887–1892 (2006).

    CAS  Article  Google Scholar 

  13. 13.

    Sofic, E., Lange, K. W., Jellinger, K. & Riederer, P. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci. Lett. 142, 128–130 (1992).

    CAS  Article  Google Scholar 

  14. 14.

    Bergamini, M. F., Santos, A. L., Stradiotto, N. R. & Zanoni, M. V. A disposable electrochemical sensor for the rapid determination of levodopa. J. Pharm. Biomed. Anal. 39, 54–59 (2005).

    CAS  Article  Google Scholar 

  15. 15.

    Wassum, K. M. et al. Silicon wafer-based platinum microelectrode array biosensor for near real-time measurement of glutamate in vivo. Sensors 8, 5023–5036 (2008).

    CAS  Article  Google Scholar 

  16. 16.

    Contag, C. H. & Bachmann, M. H. Advances in in vivo bioluminescence imaging of gene expression. Annu. Rev. Biomed. Eng. 4, 235–260 (2002).

    CAS  Article  Google Scholar 

  17. 17.

    Weissleder, R. & Ntziachristos, V. Shedding light onto live molecular targets. Nat. Med. 9, 123–128 (2003).

    CAS  Article  Google Scholar 

  18. 18.

    Lee, A. K., Manns, I. D., Sakmann, B. & Brecht, M. Whole-cell recordings in freely moving rats. Neuron 51, 399–407 (2006).

    CAS  Article  Google Scholar 

  19. 19.

    Kodandaramaiah, S. B., Franzesi, G. T., Chow, B. Y., Boyden, E. S. & Forest, C. R. Automated whole-cell patch-clamp electrophysiology of neurons in vivo. Nat. Methods 9, 585–587 (2012).

    CAS  Article  Google Scholar 

  20. 20.

    Hochberg, L. R. et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–171 (2006).

    CAS  Article  Google Scholar 

  21. 21.

    Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotech. 8, 83–94 (2013).

    CAS  Article  Google Scholar 

  22. 22.

    Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl Acad. Sci. USA 100, 7319–7324 (2003).

    CAS  Article  Google Scholar 

  23. 23.

    Flusberg, B. A. et al. Fiber-optic fluorescence imaging. Nat. Methods 2, 941–950 (2005).

    CAS  Article  Google Scholar 

  24. 24.

    Seo, D., Carmena, J. M., Rabaey, J. M., Maharbiz, M. M. & Alon, E. Model validation of untethered, ultrasonic neural dust motes for cortical recording. J. Neurosci. Methods 244, 114–122 (2015).

    Article  Google Scholar 

  25. 25.

    Seo, D. et al. Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91, 529–539 (2016).

    CAS  Article  Google Scholar 

  26. 26.

    Frank, S. & Lauterbur, P. C. Voltage-sensitive magnetic gels as magnetic resonance monitoring agents. Nature 363, 334–336 (1993).

    CAS  Article  Google Scholar 

  27. 27.

    Kruttwig, K. et al. Reversible low-light induced photoswitching of crowned spiropyran-DO3A complexed with gadolinium (III) ions. Molecules 17, 6605–6624 (2012).

    CAS  Article  Google Scholar 

  28. 28.

    Louie, A. Multimodality imaging probes: design and challenges. Chem. Rev. 110, 3146–3195 (2010).

    CAS  Article  Google Scholar 

  29. 29.

    Weis, R., Müller, B. & Fromherz, P. Neuron adhesion on a silicon chip probed by an array of field-effect transistors. Phys. Rev. Lett. 76, 327–330 (1996).

    CAS  Article  Google Scholar 

  30. 30.

    Cohen, A. et al. Depletion type floating gate p-channel MOS transistor for recording action potentials generated by cultured neurons. Biosens. Bioelectron. 19, 1703–1709 (2004).

    CAS  Article  Google Scholar 

  31. 31.

    Lorach, H. et al. Photovoltaic restoration of sight with high visual acuity. Nat. Med. 21, 476–482 (2015).

    CAS  Article  Google Scholar 

  32. 32.

    Palanker, D., Vankov, A., Huie, P. & Baccus, S. Design of a high-resolution optoelectronic retinal prosthesis. J. Neural Eng. 2, S105–S120 (2005).

    Article  Google Scholar 

  33. 33.

    Luo, X.-L., Xu, J.-J., Zhao, W. & Chen, H.-Y. Glucose biosensor based on ENFET doped with SiO2nanoparticles. Sens. Actuators B 97, 249–255 (2004).

    CAS  Article  Google Scholar 

  34. 34.

    Miyahara, Y., Moriizumi, T. & Ichimura, K. Integrated enzyme FETs for simultaneous detections of urea and glucose. Sens. Actuators 7, 1–10 (1985).

    CAS  Article  Google Scholar 

  35. 35.

    Hai, A. et al. Acetylcholinesterase-ISFET based system for the detection of acetylcholine and acetylcholinesterase inhibitors. Biosens. Bioelectron. 22, 605–612 (2006).

    CAS  Article  Google Scholar 

  36. 36.

    Lyons, S. K. et al. Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer Res. 66, 4701–4707 (2006).

    CAS  Article  Google Scholar 

  37. 37.

    Evans, M. S. et al. A synthetic luciferin improves bioluminescence imaging in live mice. Nat. Methods 11, 393–395 (2014).

    CAS  Article  Google Scholar 

  38. 38.

    Juchem, C. & de Graaf, R. A. B0 magnetic field homogeneity and shimming for in vivo magnetic resonance spectroscopy. Anal. Biochem. 529, 17–29 (2017).

    CAS  Article  Google Scholar 

  39. 39.

    Center for Devices and Radiological Health Criteria for Significant Risk Investigations of Magnetic Resonance Diagnostic Devices (US Food and Drug Administration, 2014).

  40. 40.

    Iwano, S. et al. Single-cell bioluminescence imaging of deep tissue in freely moving animals. Science 359, 935–939 (2018).

    CAS  Article  Google Scholar 

  41. 41.

    Ho, J. S. et al. Wireless power transfer to deep-tissue microimplants. Proc. Natl Acad. Sci. USA 111, 7974–7979 (2014).

    CAS  Article  Google Scholar 

  42. 42.

    Lee, H., Sun, E., Ham, D. & Weissleder, R. Chip-NMR biosensor for detection and molecular analysis of cells. Nat. Med. 14, 869–874 (2008).

    Article  Google Scholar 

  43. 43.

    Haun, J. B. et al. Micro-NMR for rapid molecular analysis of human tumor samples. Sci. Transl. Med. 3, 71ra16 (2011).

    Article  Google Scholar 

  44. 44.

    Kratt, K., Badilita, V., Burger, T., Korvink, J. & Wallrabe, U. A fully MEMS-compatible process for 3D high aspect ratio micro coils obtained with an automatic wire bonder. J. Micromech. Microeng. 20, 015021 (2009).

    Article  Google Scholar 

  45. 45.

    Fischer, A. C. et al. Unconventional applications of wire bonding create opportunities for microsystem integration. J. Micromech. Microeng. 23, 083001 (2013).

    Article  Google Scholar 

  46. 46.

    Feiner, R. & Dvir, T. Tissue–electronics interfaces: from implantable devices to engineered tissues. Nat. Rev. Mater. 3, 17076 (2017).

    Article  Google Scholar 

  47. 47.

    Eidmann, G., Savelsberg, R., Blümler, P. & Blümich, B. The NMR MOUSE, a mobile universal surface explorer. J. Magn. Reson. 122, 104–109 (1996).

    CAS  Article  Google Scholar 

  48. 48.

    Demas, V. et al. Three-dimensional phase-encoded chemical shift MRI in the presence of inhomogeneous fields. Proc. Natl Acad. Sci. USA 101, 8845–8847 (2004).

    CAS  Article  Google Scholar 

  49. 49.

    Cooley, C. Z. et al. Design of sparse Halbach magnet arrays for portable MRI using a genetic algorithm. IEEE Trans. Magn. 54, 1–12 (2018).

    Article  Google Scholar 

  50. 50.

    Negrin, R. S. & Contag, C. H. In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease. Nat. Rev. Immunol. 6, 484–490 (2006).

    CAS  Article  Google Scholar 

  51. 51.

    Naumann, E. A., Kampff, A. R., Prober, D. A., Schier, A. F. & Engert, F. Monitoring neural activity with bioluminescence during natural behavior. Nat. Neurosci. 13, 513–520 (2010).

    CAS  Article  Google Scholar 

  52. 52.

    Hai, A. et al. Changing gears from chemical adhesion of cells to flat substrata toward engulfment of micro-protrusions by active mechanisms. J. Neural Eng. 6, 066009 (2009).

    Article  Google Scholar 

  53. 53.

    Hai, A. et al. Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices. J. R. Soc. Interface. 6, 1153–1165 (2009).

    CAS  Article  Google Scholar 

  54. 54.

    Hai, A., Shappir, J. & Spira, M. E. In-cell recordings by extracellular microelectrodes. Nat. Methods 7, 200–202 (2010).

    CAS  Article  Google Scholar 

  55. 55.

    Hai, A., Shappir, J. & Spira, M. E. Long-term, multisite, parallel, in-cell recording and stimulation by an array of extracellular microelectrodes. J. Neurophysiol. 104, 559–568 (2010).

    CAS  Article  Google Scholar 

  56. 56.

    Katz, E. & Willner, I. Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy: routes to impedimetric immunosensors, DNA‐sensors, and enzyme biosensors. Electroanalysis 15, 913–947 (2003).

    CAS  Article  Google Scholar 

  57. 57.

    Hai, A., Cai, L. X., Lee, T., Lelyveld, V. S. & Jasanoff, A. Molecular fMRI of serotonin transport. Neuron 92, 754–765 (2016).

    CAS  Article  Google Scholar 

Download references


This research was funded by NIH grants R01 NS76462, R01 DA038642 and U01 NS904051 to A.J. A.H. was supported by postdoctoral fellowships from the Edmond & Lily Safra Center for Brain Sciences and a long-term fellowship of the European Molecular Biology Organization. We thank A. Takahashi for assistance with 3 T MRI measurements.

Author information




A.H. and A.J. devised the ImpACT concept. A.H., V.C.S., B.B.B. and A.J. designed the research. A.H. performed the modelling calculations. A.H. and V.C.S. performed the in vitro measurements and analysed the data. A.H. and B.B.B. performed the in vivo imaging experiments. A.H. and A.J. wrote the manuscript.

Corresponding author

Correspondence to Alan Jasanoff.

Ethics declarations

Competing interests

MIT has filed a provisional patent application related to this technology.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Text and Supplementary Figures

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hai, A., Spanoudaki, V.C., Bartelle, B.B. et al. Wireless resonant circuits for the minimally invasive sensing of biophysical processes in magnetic resonance imaging. Nat Biomed Eng 3, 69–78 (2019). https://doi.org/10.1038/s41551-018-0309-8

Download citation

Further reading