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Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant

Nature Biotechnology volume 39, pages 855–864 (2021)Cite this article

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Abstract

Vascular complications following solid organ transplantation may lead to graft ischemia, dysfunction or loss. Imaging approaches can provide intermittent assessments of graft perfusion, but require highly skilled practitioners and do not directly assess graft oxygenation. Existing systems for monitoring tissue oxygenation are limited by the need for wired connections, the inability to provide real-time data or operation restricted to surface tissues. Here, we present a minimally invasive system to monitor deep-tissue O2 that reports continuous real-time data from centimeter-scale depths in sheep and up to a 10-cm depth in ex vivo porcine tissue. The system is composed of a millimeter-sized, wireless, ultrasound-powered implantable luminescence O2 sensor and an external transceiver for bidirectional data transfer, enabling deep-tissue oxygenation monitoring for surgical or critical care indications.

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Fig. 1: Wireless O2-monitoring system overview.
Fig. 2: Biocompatible O2-sensing film, operating principle of the luminescence O2 sensor and its optical characterization.
Fig. 3: Entirely wireless O2-monitoring system block diagram.
Fig. 4: In vitro characterization of the wireless O2-sensing system.
Fig. 5: Surgical placement of and recording from the implantable, wireless O2 sensor under conditions of normoxia, hyperoxia and hypoxia.
Fig. 6: In vitro and ex vivo uplink characterization of the wireless O2-sensing system.

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Data availability

All data supporting the results in this study are available within the article or its Supplementary Information.

Code availability

The custom Labview program and Matlab code used in this study are available on Github at https://github.com/ssonmezoglu/NBT-21.

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Acknowledgements

This work was supported by the Chan Zuckerberg Biohub (CZB) (to M.M.M.) and by NIH/NICHD R44HD094414 and R01HD072455 (to J.R.F. and E.M.). We thank C. Losser, R. Hutchings and C. Vento for expert assistance with animal handling and surgery as well as members of the Laboratory Animal Resource Center (LARC) at the University of California, San Francisco. We also thank the Berkeley Wireless Research Center and R. Muller (University of California, Berkeley) for access to IC design software.

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Authors and Affiliations

  1. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA

    Soner Sonmezoglu & Michel M. Maharbiz

  2. Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA

    Jeffrey R. Fineman & Emin Maltepe

  3. Initiative for Pediatric Drug and Device Development, San Francisco, CA, USA

    Jeffrey R. Fineman & Emin Maltepe

  4. The UC Berkeley–UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA

    Michel M. Maharbiz

  5. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Michel M. Maharbiz

Authors
  1. Soner Sonmezoglu
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  2. Jeffrey R. Fineman
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Contributions

S.S. supervised the project, designed and built the wireless system, designed and performed the in vitro and ex vivo experiments and analyzed and interpreted the associated data. S.S., J.R.F. and E.M. designed and performed the in vivo experiments and interpreted biological data. M.M.M. contributed to the design of the experiments. S.S., E.M. and M.M.M. participated in writing the paper. All authors contributed to the discussion of the paper.

Corresponding authors

Correspondence to Soner Sonmezoglu or Michel M. Maharbiz.

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Competing interests

M.M.M. is an employee of iota Biosciences, Inc., a fully owned subsidiary of Astellas Pharma. All of the other authors declare no competing interests.

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Sonmezoglu, S., Fineman, J.R., Maltepe, E. et al. Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant. Nat Biotechnol 39, 855–864 (2021). https://doi.org/10.1038/s41587-021-00866-y

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