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Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow

Nature Biomedical Engineering volume 3, pages 47–57 (2019)Cite this article

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Abstract

The ability to monitor blood flow is critical to patient recovery and patient outcomes after complex reconstructive surgeries. Clinically available wired implantable monitoring technology requires careful fixation for accurate detection and needs to be removed after use. Here, we report the design of a pressure sensor, made entirely of biodegradable materials and based on fringe-field capacitor technology, for measuring arterial blood flow in both contact and non-contact modes. The sensor is operated wirelessly through inductive coupling, has minimal hysteresis, fast response times, excellent cycling stability, is highly robust, allows for easy mounting and eliminates the need for removal, thus reducing the risk of vessel trauma. We demonstrate the operation of the sensor with a custom-made artificial artery model and in vivo in rats. This technology may be advantageous in real-time post-operative monitoring of blood flow after reconstructive surgery.

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Fig. 1: Biodegradable, flexible and passive arterial-pulse sensor design.
Fig. 2: Wireless link design, simulation and optimization.
Fig. 3: Fringe-field capacitive sensor design and optimization.
Fig. 4: In vitro sensor characterization using an artificial artery model.
Fig. 5: In vivo sensor characterization.

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Data availability

The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information. Raw data generated for this study are available from the corresponding author on reasonable request.

References

  1. Regenbogen, S. E. et al. Costs and consequences of early hospital discharge after major inpatient surgery in older adults. JAMA Surg. 152, e170123 (2017).

    Article  Google Scholar 

  2. Smit, J. M. Advancements in free flap monitoring in the last decade: a critical review. Plast. Reconstr. Surg. 125, 177–185 (2010).

    Article  CAS  Google Scholar 

  3. Lin, S. J. et al. Tissue oximetry monitoring in microsurgical breast reconstruction decreases flap loss and improves rate of flap salvage. Plast. Reconstr. Surg. 127, 1080–1085 (2011).

    Article  CAS  Google Scholar 

  4. Swartz, W. M., Jones, N. F., Cherup, L. & Klein, A. Direct monitoring of microvascular anastomoses with the 20-MHz ultrasonic Doppler probe: an experimental and clinical study. Plast. Reconstr. Surg. 81, 149–161 (1988).

    Article  CAS  Google Scholar 

  5. Bill, T. J., Foresman, P. A., Rodeheaver, G. T. & Drake, D. B. Fibrin sealant: a novel method of fixation for an implantable ultrasonic microDoppler probe. J. Reconstr. Microsurg. 17, 257–262 (2001).

    Article  CAS  Google Scholar 

  6. Whitaker, I. S., Smit, J. M. & Acosta, R. A simple method of implantable Doppler cuff attachment: experience in 150 DIEP breast reconstructions. J. Plast. Reconstr. Aesthet. Surg. 61, 1251–1252 (2008).

    Article  Google Scholar 

  7. Smit, J. M. et al. Post operative monitoring of microvascular breast reconstructions using the implantable Cook–Swartz Doppler system: a study of 145 probes & technical discussion. J. Plast. Reconstr. Aest. Surg. 62, 1286–1292 (2009).

    Article  CAS  Google Scholar 

  8. Ruhhammer, J. et al. Magnetic sensor for monitoring of arterial strain. In 2013 Transducers & Eurosensors XXVII (2013).

  9. Seres, L., Makula, E., Morvay, Z. & Borbely, L. Color Doppler ultrasound for monitoring free flaps in the head and neck region. J. Craniofac. Surg. 13, 75–78 (2002).

    Article  Google Scholar 

  10. Few, J. W., Corral, C. J., Fine, N. A. & Dumanian, G. A. Monitoring buried head and neck free flaps with high-resolution colorduplex ultrasound. Plast. Reconstr. Surg. 108, 709–712 (2001).

    Article  CAS  Google Scholar 

  11. Stone, C. A., Dubbins, P. A. & Morris, R. J. Use of colour duplex Doppler imaging in the postoperative assessment of buried free flaps. Microsurgery 21, 223–227 (2001).

    Article  CAS  Google Scholar 

  12. Schon, R. et al. Color duplex sonography for the monitoring of vascularized free bone flaps. Otolaryngol. Head Neck Surg. 129, 71–76 (2003).

    Article  Google Scholar 

  13. Scheufler, O., Exner, K. & Andresen, R. Investigation of TRAM flap oxygenation and perfusion by near-infrared reflection spectroscopy and color-coded duplex sonography. Plast. Reconstr. Surg. 113, 141–155 (2004).

    Article  Google Scholar 

  14. Irwin, M. S., Thorniley, M. S., Dore, C. J. & Green, C. J. Near infra-red spectroscopy: a non-invasive monitor of perfusion and oxygenation within the microcirculation of limbs and flaps. Br. J. Plast. Surg. 48, 14–22 (1995).

    Article  CAS  Google Scholar 

  15. Repez, A., Oroszy, D. & Arnez, Z. M. Continuous postoperative monitoring of cutaneous free flaps using near infrared spectroscopy. J. Plast. Reconstr. Aesthet. Surg. 61, 71–77 (2008).

    Article  Google Scholar 

  16. Cai, Z. G. et al. Evaluation of near infrared spectroscopy in monitoring postoperative regional tissue oxygen saturation for fibular flaps. J. Plast. Reconstr. Aesthet. Surg. 61, 289–296 (2008).

    Article  Google Scholar 

  17. Delgado, J. M., DeFeudis, F. V., Roth, R. H., Ryugo, D. K. & Mitruka, B. M. Dialytrode for long term intracerebral perfusion in awake monkeys. Arch. Int. Pharmacodynam. Ther. 198, 9–21 (1972).

    CAS  Google Scholar 

  18. Rojdmark, J., Blomqvist, L., Malm, M., Adams-Ray, B. & Ungerstedt, U. Metabolism in myocutaneous flaps studied by in situ microdialysis. Scand. J. Plast. Reconstr. Surg. Hand Surg. 32, 27–34 (1998).

    Article  CAS  Google Scholar 

  19. Goodman, J. C. et al. Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis. Crit. Care Med. 27, 1965–1973 (1999).

    Article  CAS  Google Scholar 

  20. Setala, L. et al. Microdialysis detects postoperative perfusion failure in microvascular flaps. J. Reconstr. Microsurg. 22, 87–96 (2006).

    Article  Google Scholar 

  21. Holzle, F., Loeffelbein, D. J., Nolte, D. & Wolff, K. D. Free flap monitoring using simultaneous non-invasive laser Doppler flowmetry and tissue spectrophotometry. J. Craniomaxillofac. Surg. 34, 25–33 (2006).

    Article  Google Scholar 

  22. Heller, L., Levin, L. S. & Klitzman, B. Laser Doppler flowmeter monitoring of free-tissue transfers: blood flow in normal and complicated cases. Plast. Reconstr. Surg. 107, 1739–1745 (2001).

    Article  CAS  Google Scholar 

  23. Yuen, J. C. & Feng, Z. Monitoring free flaps using the laser Doppler flowmeter: five-year experience. Plast. Reconstr. Surg. 105, 55–61 (2000).

    Article  CAS  Google Scholar 

  24. Hallock, G. G. A. A “true” false-negative misadventure in free flap monitoring using laser Doppler flowmetry. Plast. Reconstr. Surg. 110, 1609–1611 (2002).

    Article  Google Scholar 

  25. Fu, R. et al. Implantable and biodegradable poly(l‐lactic acid) fibers for optical neural interfaces. Adv. Opt. Mater. 6, 1870010 (2018).

  26. Yu, K. J. et al. Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex. Nat. Mater. 15, 782–791 (2016).

    Article  CAS  Google Scholar 

  27. Lee, G. et al. Fully biodegradable microsupercapacitor for power storage in transient electronics, advanced energy. Adv. Energy Mater. 7, 1700157 (2017).

  28. Mahajan, B. K., Yu, X., Shou, W., Pan, H. & Huang, X. Mechanically milled irregular zinc nanoparticles for printable bioresorbable electronics. Small 13, 1700065 (2017).

  29. Chen, C. et al. Transient micromotors that disappear when no longer needed. ACS Nano 10, 10389–10396 (2016).

    Article  CAS  Google Scholar 

  30. Um, G. T. et al. Implantable Cook–Swartz Doppler probe versus Synovis Flow Coupler for the postoperative monitoring of free flap breast reconstruction. J. Plast. Reconstr. Aesthet. Surg. 67, 960–966 (2014).

    Article  Google Scholar 

  31. Chen, K. T. et al. Timing of presentation of the first signs of vascular compromise dictates the salvage outcome of free flap transfers. Plast. Reconstr. Surg. 120, 187–195 (2007).

    Article  CAS  Google Scholar 

  32. Boutry, C. M. et al. A ensitive and biodegradable pressure sensor array for cardiovascular monitoring. Adv. Mater. 27, 6954–6961 (2015).

    Article  CAS  Google Scholar 

  33. Holland, S. J., Tighe, B. J. & Gould, P. L. Polymers for biodegradable medical devices. 1. The potential of polyesters as controlled macromolecular release systems. J. Control. Release 4, 155–180 (1985).

  34. Kelly, P. & Atkins, T. W. in Microencapsulation of Drugs (Harwood Academic Publishers, 1992).

  35. Wang, Y., Ameer, G. A., Sheppard, B. J. & Langer, R. A tough biodegradable elastomer. Nat. Biotechnol. 20, 602–606 (2002).

    Article  CAS  Google Scholar 

  36. Tran, R. T. et al. Synthesis and characterization of a biodegradable elastomer featuring a dual crosslinking mechanism. Soft Matter 6, 2449–2461 (2010).

    Article  CAS  Google Scholar 

  37. Zhang, B. et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15, 669–678 (2016).

    Article  CAS  Google Scholar 

  38. Davenport-Huyer, L. et al. Highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications. ACS Biomater. Sci. Eng. 2, 780–788 (2016).

    Article  CAS  Google Scholar 

  39. Boutry, C. M. et al. A stretchable and biodegradable strain and pressure sensor for orthopedic application. Nat. Electron. 1, 314–321 (2018).

    Article  Google Scholar 

  40. Purnama, A., Hermawan, H. & Mantovani, D. Biodegradable metal stents: a focused review on materials and clinical studies. J. Biomater. Tissue Eng. 4, 868–874 (2014).

    Article  Google Scholar 

  41. Zheng, Y. F., Gu, X. N. & Witte, F. Biodegradable metals. Mater. Sci. Eng. R 77, 1–34 (2014).

    Article  Google Scholar 

  42. Yin, L. et al. Dissolvable metals for transient electronics. Adv. Funct. Mater. 24, 645–658 (2014).

    Article  CAS  Google Scholar 

  43. Chen, L. Y. et al. Continuous wireless pressure monitoring and mapping with ultra-small passive sensors for health monitoring and critical care. Nat. Commun. 5, 5028 (2014).

    Article  CAS  Google Scholar 

  44. Chen, H. & Lou, A. A study of RF power attenuation in bio-tissues. J. Med. Biol. Eng. 24, 141–146 (2004).

    Google Scholar 

  45. Donaldson, N. D. & Perkins, T. A. Analysis of resonant coupled coils in the design of radio frequency transcutaneous links. Med. Biol. Eng. Comput. 21, 612–627 (1983).

    Article  CAS  Google Scholar 

  46. Bocan, K. N. et al. Multi-disciplinary challenges in tissue modeling for wireless electromagnetic powering: a review. IEEE Sens. J. 17, 6498–6509 (2017).

    Article  CAS  Google Scholar 

  47. Cicekcibasi, A. E. et al. The mandibular landmarks about the facial artery and vein with multidetector computed tomography angiography (MDCTA): an anatomical and radiological morphometric study. Int. J. Morphol. 30, 504–509 (2012).

    Article  Google Scholar 

  48. Graf., S. et al. Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing. Ultrasound Med. Biol. 25, 1353–1363 (1999).

    Article  CAS  Google Scholar 

  49. Zhao, Y. P. et al. Color Doppler sonography of the facial artery. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 93, 195–201 (2002).

  50. Nair, N. R. et al. in Current Developments in Biotechnology and Bioengineering Production, Isolation and Purification of Industrial Products 739–755 (2017).

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

    Article  Google Scholar 

  52. Brennan, J. F. et al. Determination of human coronary artery composition by Raman spectroscopy. Circulation 96, 99–105 (1997).

    Article  CAS  Google Scholar 

  53. Gamble, G., Zorn, J., Sanders, G., MacMahon, S. & Sharpe, N. Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound measurements of the common carotid artery. Stroke 25, 11–16 (1994).

    Article  CAS  Google Scholar 

  54. Chortos, A., Liu, J. & Bao, Z. Pursuing prosthetic electronic skin. Nat. Mater. 15, 937–950 (2016).

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Acknowledgements

C.M.B. acknowledges postdoctoral fellowship support from the Swiss National Science Foundation (postdoc mobility fellowship no. P2EZP2_152118) and the European Commission (Marie Curie international outgoing fellowship grant no. 622362). L.B. and Y.K. acknowledge the Stanford ChEM-H Postdocs at the Interface seed grant. Part of this work was performed at the Stanford Nano Shared Facilities. A.C.H. acknowledges support from the National Science Foundation Graduate Research Fellowship (grant no. DGE-1147474).

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Author notes

  1. These authors contributed equally: Clementine M. Boutry, Levent Beker.

Authors and Affiliations

  1. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Clementine M. Boutry, Levent Beker, Helen Tran, Allison C. Hinckley, Raphael Pfattner, Simiao Niu, Junheng Li, Jean Claverie & Zhenan Bao

  2. Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA

    Yukitoshi Kaizawa, Zhen Wang, James Chang & Paige M. Fox

  3. Division of Plastic Surgery, Veterans Affairs Palo Alto, Palo Alto, CA, USA

    Yukitoshi Kaizawa, Zhen Wang, James Chang & Paige M. Fox

  4. Department of Electrical Engineering, Stanford University, Stanford, CA, USA

    Christopher Vassos

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Contributions

C.M.B. and L.B. were the main contributors to this work and were responsible for elaboration of the sensor concept, development of new fabrication processes, performing all experiments for investigations into the materials, characterization of devices, data collection for in vitro experiments, data analysis and interpretation, and drafting of the article. L.B. and Y.K. performed the in vivo experiments. Y.K. performed implantation surgeries related to the in vivo studies, which included the design of the in vivo studies, development of the protocols, sensor implantation, operation studies and material biocompatibility studies. Y.K. also worked on data analysis and interpretation. C.V. contributed with the design of the LCR wireless sensor and performed all of the Computer Simulation Technology simulations. H.T. synthesized the biodegradable materials. A.C.H. and R.P. developed a new fabrication set-up for the fabrication of the Mg interconnect and provided critical revisions of the article. S.N. provided the initial Comsol simulations. J.L. and J.Cl. participated in the elaboration of the sensor concept, development of new fabrication processes and fabrication of the sensor. Z.W., J.Ch. and P.M.F. contributed to the design of the in vivo studies, working on the protocols and data interpretation. Y.K., P.M.F. and C.V. also contributed to the drafting and critical revision of the article. Z.B. contributed to the development of the sensor concept, fabrication processes, investigations of the materials, characterization of the devices, data interpretation and critical revisions of the article.

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Correspondence to Paige M. Fox.

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Stanford University has filed a provisional patent application (62750518) related to this technology.

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Supplementary information

Supplementary Information

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Reporting Summary

Supplementary Video 1

Heart-pulse-rate measurement via external Doppler ultrasound during in vivo characterization

Supplementary Video 2

After 12 weeks of sensor implantation, the rat was able to move without any apparent limb impairment

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Boutry, C.M., Beker, L., Kaizawa, Y. et al. Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow. Nat Biomed Eng 3, 47–57 (2019). https://doi.org/10.1038/s41551-018-0336-5

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