Biomedical Microdevices

, 18:38 | Cite as

Nanofiber-based paramagnetic probes for rapid, real-time biomedical oximetry

  • Vidya P. Bhallamudi
  • Ruipeng Xue
  • Carola M. Purser
  • Kayla F Presley
  • Yeshavanth K. Banasavadi-Siddegowda
  • Jinwoo Hwang
  • Balveen Kaur
  • P. Chris Hammel
  • Michael G. Poirier
  • John J. Lannutti
  • Ramasamy P. Pandian
Article

Abstract

EPR (electron paramagnetic resonance) based biological oximetry is a powerful tool that accurately and repeatedly measures tissue oxygen levels. In vivo determination of oxygen in tissues is crucial for the diagnosis and treatment of a number of diseases. Here, we report the first successful fabrication and remarkable properties of nanofiber sensors for EPR-oximetry applications. Lithium octa-n-butoxynaphthalocyanine (LiNc- BuO), an excellent paramagnetic oxygen sensor, was successfully encapsulated in 300–500 nm diameter fibers consisting of a core of polydimethylsiloxane (PDMS) and a shell of polycaprolactone (PCL) by electrospinning. This core–shell nanosensor (LiNc-BuO-PDMS-PCL) shows a linear dependence of linewidth versus oxygen partial pressure (pO2). The nanofiber sensors have response and recovery times of 0.35 s and 0.55 s, respectively, these response and recovery times are ~12 times and ~218 times faster than those previously reported for PDMS-LiNc-BuO chip sensors. This greater responsiveness is likely due to the high porosity and excellent oxygen permeability of the nanofibers. Electrospinning of the structurally flexible PDMS enabled the fabrication of fibers having tailored spin densities. Core-shell encapsulation ensures the non-exposure of embedded LiNc-BuO and mitigates potential biocompatibility concerns. In vitro evaluation of the fiber performed under exposure to cultured cells showed that it is both stable and biocompatible. The unique combination of biocompatibility due to the PCL ‘shell,’ the excellent oxygen transparency of the PDMS core, and the excellent oxygen-sensing properties of LiNc-BuO makes LiNc-BuO-PDMS-PCL platform promising for long-term oximetry and repetitive oxygen measurements in both biological systems and clinical applications.

Keywords

Naphthalocyanine Paramagnetic materials Spin probe Oxygen sensing EPR oximetry Electrospun fiber 

References

  1. M. Afeworki, N. R. Miller, N. Devasahayam, J. Cook, J. B. Mitchell, S. Subramanian, M. C. Krishna, Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric probe. Free Radic. Biol. Med. 25(1), 72–78 (1998)CrossRefGoogle Scholar
  2. R. Ahmad, P. Kuppusamy, Theory, instrumentation, and applications of electron paramagnetic resonance oximetry. Chem. Rev. 110(5), 3212–3236 (2010)CrossRefGoogle Scholar
  3. J. M. Brown, W. R. William, Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer 4(6), 437–447 (2004)CrossRefGoogle Scholar
  4. B. A. DeGraff, J. N. Demas, Luminescence-based oxygen sensors. Rev. Fluores. 2005, 125–151 (2005)CrossRefGoogle Scholar
  5. A. Dinguizli, S. Jeumont, N. Beghein, J. He, T. Walczak, P. N. Lesniewski, H. Hou, O. Y. Grinberg, A. Sucheta, H. M. Swartz, B. Gallez, Development and evaluation of biocompatible films of polytetrafluoroethylene polymers holding lithium phthalocyanine crystals for their use in EPR oximetry. Biosens. Bioelectron. 21(7), 1015–1022 (2006)CrossRefGoogle Scholar
  6. M. Dinguizli, N. Beghein, B. Gallez, Retrievable micro-inserts containing oxygen sensors for monitoring tissue oxygenation using EPR oximetry. Physiol. Meas. 29(11), 1247–1254 (2008)CrossRefGoogle Scholar
  7. E. Eteshola, R. P. Pandian, S. C. Lee, P. Kuppusamy, Polymer coating of paramagnetic particulates for in vivo oxygen-sensing applications. Biomed. Microdevices 11(2), 379–387 (2009)CrossRefGoogle Scholar
  8. B. Gallez, B. F. Jordan, C. Baudelet, Microencapsulation of paramagnetic particles by pyrroxylin to preserve their responsiveness to oxygen when used as sensors for in vivo EPR oximetry. Magn. Reson. Med. 42(1), 193–196 (1999)CrossRefGoogle Scholar
  9. G. M. Gordillo, R. Schlanger, W. A. Wallace, V. Bergdall, R. Bartlett, C. K. Sen, Protocols for topical and systemic oxygen treatments in wound healing. Methods Enzymol. 381, 575–585 (2004)CrossRefGoogle Scholar
  10. L. H. Gray, A. D. Conger, M. Ebert, S. Hornsey, O. C. A. Scott, The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Brit. J. Radiol. 26(312), 638–648 (1953)CrossRefGoogle Scholar
  11. J. R. Griffiths, S. P. Robinson, The OxyLite: a fibre-optic oxygen sensor. Brit. J. Radiol. 72(859), 627–630 (1999)CrossRefGoogle Scholar
  12. M. Hashem, M. Weiler-Sagie, P. Kuppusamy, G. Neufeld, M. Neeman, A. Blank, Electron spin resonance microscopic imaging of oxygen concentration in cancer spheroids. J. Magn. Reson. 256, 77–85 (2015)CrossRefGoogle Scholar
  13. J. He, N. Beghein, R. B. Clarkson, H. M. Swartz, B. Gallez, Microencapsulation of carbon particles used as oxygen sensors in EPR oximetry to stabilize their responsiveness to oxygen in vitro and in vivo. Phys. Med. Biol. 46(12), 3323–3329 (2001)CrossRefGoogle Scholar
  14. M. Heyboer 3rd, S. Jennings, W. D. Grant, C. Ojevwe, J. Byrne, S. M. Wojcik, Seizure incidence by treatment pressure in patients undergoing hyperbaric oxygen therapy. Undersea Hyperb. Med. 41(5), 379–385 (2014)Google Scholar
  15. M. Hockel, K. Schlenger, M. Mitze, U. Schaffer, P. Vaupel, Hypoxia and radiation response in human tumors. Semin. Radiat. Oncol. 6(1), 3–9 (1996)CrossRefGoogle Scholar
  16. H. W. Hopf, M. D. Rollins, Wounds: an overview of the role of oxygen. Antioxid. Redox Signal. 9(8), 1183–1192 (2007)CrossRefGoogle Scholar
  17. H. W. Hopf, J. J. Gibson, A. P. Angeles, J. S. Constant, J. J. Feng, M. D. Rollins, M. Z. Hussain, T. K. Hunt, Hyperoxia and angiogenesis. Wound Repair Regen. 13(6), 558–564 (2005)CrossRefGoogle Scholar
  18. G. Ilangovan, J. L. Zweier, P. Kuppusamy, Electrochemical preparation and EPR studies of lithium phthalocyanine. Part 2: Particle-size-dependent line broadening by molecular oxygen and its implications as an oximetry probe. J. Phys. Chem. B 104(40), 9404–9410 (2000)CrossRefGoogle Scholar
  19. G. Ilangovan, H. Q. Li, J. L. Zweier, P. Kuppusamy, Electrochemical preparation and EPR studies of lithium phthalocyanine. 3. Measurements of oxygen concentration in tissues and biochemical reactions. J. Phys. Chem. B 105(22), 5323–5330 (2001)CrossRefGoogle Scholar
  20. G. Ilangovan, A. Manivannan, H. Q. Li, H. Yanagi, J. L. Zweier, P. Kuppusamy, A naphthalocyanine-based EPR probe for localized measurements of tissue oxygenation. Free Radic. Biol. Med. 32(2), 139–147 (2002a)CrossRefGoogle Scholar
  21. G. Ilangovan, R. Pal, J. L. Zweier, P. Kuppusamy, Electrochemical preparation and EPR studies of lithium phthalocyanine. 4. Effect of nitric oxide. J. Phys. Chem. B 106(46), 11929–11935 (2002b)CrossRefGoogle Scholar
  22. N. Khan, H. Hou, H. M. Swartz, P. Kuppusamy, Direct and repeated measurement of heart and brain oxygenation using in vivo EPR oximetry. Methods Enzymol. 564, 529–552 (2015)CrossRefGoogle Scholar
  23. Y. Kim, B. O. Cho, W. H. Park, Electrospinning of poly(dimethyl siloxane) by sol–gel method. J. Appl. Polym. Sci. 114(6), 3870–3874 (2009)CrossRefGoogle Scholar
  24. A. C. Kulkarni, P. Kuppusamy, N. Parinandi, Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy. Antioxid. Redox Signal. 9(10), 1717–1730 (2007)CrossRefGoogle Scholar
  25. V. K. Kutala, N. L. Parinandi, R. P. Pandian, P. Kuppusamy, Simultaneous measurement of oxygenation in intracellular and extracellular compartments of lung microvascular endothelial cells. Antioxid. Redox Signal. 6(3), 597–603 (2004)CrossRefGoogle Scholar
  26. V. K. Kutala, M. Khan, M. G. Angelos, P. Kuppusamy, Role of oxygen in postischemic myocardial injury. Antioxid. Redox Signal. 9(8), 1193–1206 (2007)CrossRefGoogle Scholar
  27. J. Lannutti, D. Reneker, T. Ma, D. Tomasko, D. F. Farson, Electrospinning for tissue engineering scaffolds. Mat. Sci. Eng C-Bio S 27(3), 504–509 (2007)CrossRefGoogle Scholar
  28. K. J. Liu, P. Gast, M. Moussavi, S. W. Norby, N. Vahidi, T. Walczak, M. Wu, H. M. Swartz, Lithium phthalocyanine - a probe for electron-paramagnetic-resonance oximetry in viable biological-systems. P. Natl. Acad. Sci USA 90(12), 5438–5442 (1993)CrossRefGoogle Scholar
  29. S. P. Marso, W. R. Hiatt, Peripheral arterial disease in patients with diabetes. J. Am. Coll. Cardiol. 47(5), 921–929 (2006)CrossRefGoogle Scholar
  30. G. Meenakshisundaram, E. Eteshola, R. P. Pandian, A. Bratasz, S. C. Lee, P. Kuppusamy, Fabrication and physical evaluation of a polymer-encapsulated paramagnetic probe for biomedical oximetry. Biomed. Microdevices 11(4), 773–782 (2009a)CrossRefGoogle Scholar
  31. G. Meenakshisundaram, E. Eteshola, R. P. Pandian, A. Bratasz, K. Selvendiran, S. C. Lee, M. C. Krishna, H. M. Swartz, P. Kuppusamy, Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation. Biomed. Microdevices 11(4), 817–826 (2009b)CrossRefGoogle Scholar
  32. G. Meenakshisundaram, R. P. Pandian, E. Eteshola, S. C. Lee, P. Kuppusamy, A paramagnetic implant containing lithium naphthalocyanine microcrystals for high-resolution biological oximetry. J. Magn. Reson. 203(1), 185–189 (2010)CrossRefGoogle Scholar
  33. R. Ogrin, M. Woodward, G. Sussman, Z. Khalil, Oxygen tension assessment: an overlooked tool for prediction of delayed healing in a clinical setting. Int. Wound J. 8(5), 437–445 (2011)CrossRefGoogle Scholar
  34. R. P. Pandian, P. Kuppusamy, Lithiated phthalocyanines: a new class of crystalline paramagnetic probes for targeted cellular oximetry and imaging by EPR spectroscopy. Biophys. J. 86(1), 191A–191A (2004)CrossRefGoogle Scholar
  35. R. P. Pandian, N. L. Parinandi, G. Ilangovan, J. L. Zweier, P. Kuppusamy, Novel particulate spin probe for targeted determination of oxygen in cells and tissues. Free Radic. Biol. Med. 35(9), 1138–1148 (2003)CrossRefGoogle Scholar
  36. R. P. Pandian, Y. I. Kim, P. M. Woodward, J. L. Zweier, P. T. Manoharan, P. Kuppusamy, The open molecular framework of paramagnetic lithium octabutoxynaphthalocyanine: implications for the detection of oxygen and nitric oxide using EPR spectroscopy. J. Mater. Chem. 16(36), 3609–3618 (2006)CrossRefGoogle Scholar
  37. R. P. Pandian, M. Dolgos, V. Dang, J. Z. Sostaric, P. M. Woodward, P. Kuppusamy, Structure and oxygen-sensing paramagnetic properties of a new lithium 1,8,15,22-tetraphenoxyphthalocyanine radical probe for biological oximetry. Chem. Mater. 19(14), 3545–3552 (2007)CrossRefGoogle Scholar
  38. R. P. Pandian, M. Dolgos, C. Marginean, P. M. Woodward, P. C. Hammel, P. T. Manoharan, P. Kuppusamy, Molecular packing and magnetic properties of lithium naphthalocyanine crystals: hollow channels enabling permeability and paramagnetic sensitivity to molecular oxygen. J. Mater. Chem. 19(24), 4138–4147 (2009)CrossRefGoogle Scholar
  39. R. P. Pandian, G. Meenakshisundaram, A. Bratasz, E. Eteshola, S. C. Lee, P. Kuppusamy, An implantable Teflon chip holding lithium naphthalocyanine microcrystals for secure, safe, and repeated measurements of pO(2) in tissues. Biomed. Microdevices 12(3), 381–387 (2010a)CrossRefGoogle Scholar
  40. R. P. Pandian, N. P. Raju, J. C. Gallucci, P. M. Woodward, A. J. Epstein, P. Kuppusamy, A new tetragonal crystalline polymorph of lithium octa-n-butoxy-naphthalocyanine (LiNc-BuO) radical: structural, Magnetic and oxygen-sensing properties. Chem. Mater. 22(23), 6254–6262 (2010b)CrossRefGoogle Scholar
  41. R. D. Ratner, A. S. Hoffman, F. J. Schoen, J. E. Lemons, Biomaterials Science: An Introduction to Materials in Medicine, second edn. (Elsevier Academic Press, Waltham, 2004)Google Scholar
  42. D. H. Reneker, A. L. Yarin, E. Zussman, H. Xu, Electrospinning of nanofibers from polymer solutions and melts. Adv. Appl. Mech. 41, 43–195 (2007)CrossRefGoogle Scholar
  43. R. D. Restrepo, K. R. Hirst, L. Wittnebel, R. Wettstein, AARC clinical practice guideline: transcutaneous monitoring of carbon dioxide and oxygen: 2012. Respir. Care 57(11), 1955–1962 (2012)CrossRefGoogle Scholar
  44. H. M. Swartz, B. B. Williams, R. J. Nicolalde, E. Demidenko, A. B. Flood, Overview of biodosimetry for management of unplanned exposures to ionizing radiation. Radiat. Meas. 46(9), 742–748 (2011)CrossRefGoogle Scholar
  45. H. M. Swartz, H. Hou, N. Khan, L. A. Jarvis, E. Y. Chen, B. B. Williams, P. Kuppusamy, Advances in probes and methods for clinical EPR oximetry. Adv. Exp. Med. Biol. 812, 73–79 (2014a)CrossRefGoogle Scholar
  46. H. M. Swartz, B. B. Williams, B. I. Zaki, A. C. Hartford, L. A. Jarvis, E. Y. Chen, R. J. Comi, M. S. Ernstoff, H. G. Hou, N. Khan, S. G. Swarts, A. B. Flood, P. Kuppusamy, Clinical EPR: unique opportunities and some challenges. Acad. Radiol. 21(2), 197–206 (2014b)CrossRefGoogle Scholar
  47. P. Vaupel, A. Mayer, Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 26(2), 225–239 (2007)CrossRefGoogle Scholar
  48. P. Vaupel, M. Hockel, A. Mayer, Detection and characterization of tumor hypoxia using pO2 histography. Antioxid. Redox Signal. 9(8), 1221–1235 (2007)CrossRefGoogle Scholar
  49. X. Wang, H. Chen, Y. Zhao, X. Chen, X. Wang, Optical oxygen sensors move towards colorimetric determination. Trends Anal. Chem. 29, 319–338 (2010)CrossRefGoogle Scholar
  50. S. Wisel, S. M. Chacko, M. L. Kuppusamy, R. P. Pandian, M. Khan, V. K. Kutala, R. W. Burry, B. Sun, P. Kwiatkowski, P. Kuppusamy, Labeling of skeletal myoblasts with a novel oxygen-sensing spin probe for noninvasive monitoring of in situ oxygenation and cell therapy in heart. Am. J. Physiol-Heart C 292(3), H1254–H1261 (2007)CrossRefGoogle Scholar
  51. R. P. Xue, P. Behera, M. S. Viapiano, J. J. Lannutti, Rapid response oxygen-sensing nanofibers. Mat. Sci. Eng C-Mater. 33(6), 3450–3457 (2013)CrossRefGoogle Scholar
  52. R. P. Xue, P. Behera, J. S. Xu, M. S. Viapiano, J. J. Lannutti, Polydimethylsiloxane core-polycaprolactone shell nanofibers as biocompatible, real-time oxygen sensors. Sensors Actuators B Chem. 192, 697–707 (2014)CrossRefGoogle Scholar
  53. X. Zhao, G. L. He, Y. R. Chen, R. P. Pandian, P. Kuppusamy, J. L. Zweier, Endothelium-derived nitric oxide regulates postischemic myocardial oxygenation and oxygen consumption by modulation of mitochondrial electron transport. Circulation 111(22), 2966–2972 (2005)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Vidya P. Bhallamudi
    • 1
  • Ruipeng Xue
    • 2
  • Carola M. Purser
    • 1
  • Kayla F Presley
    • 2
  • Yeshavanth K. Banasavadi-Siddegowda
    • 3
  • Jinwoo Hwang
    • 2
  • Balveen Kaur
    • 3
  • P. Chris Hammel
    • 1
  • Michael G. Poirier
    • 1
  • John J. Lannutti
    • 2
  • Ramasamy P. Pandian
    • 1
  1. 1.Department of PhysicsThe Ohio State UniversityColumbusUSA
  2. 2.Department of Materials Science and EngineeringThe Ohio State UniversityColumbusUSA
  3. 3.Department of NeurosurgeryThe Ohio State UniversityColumbusUSA

Personalised recommendations