Annals of Biomedical Engineering

, Volume 36, Issue 1, pp 30–40 | Cite as

Enabling Sensor Technologies for the Quantitative Evaluation of Engineered Tissue

Article

Abstract

Research in regenerative medicine has necessitated the need for advanced sensing technologies to monitor and evaluate the quality of engineered tissues. Several sensing schemes have been developed to sense specific analytes that enable researchers to assess tissue morphology, growth, and function. In addition to microscopy and staining techniques, tissue engineers are presented with an array of optical, chemical, and biological sensor technologies, which provide them with an opportunity to monitor variables, such as oxygen concentration, pH value, carbon dioxide, and glucose concentration in a noninvasive or minimally invasive manner. The article presents a short description on the core technologies and research reviews on the use of sensors employed in tissue engineering over the past decade. The article concludes by presenting some of the challenges to the further development of these technologies that are capable of real time measurement of tissue structure, composition, and function both for in-vitro and in-vivo analysis.

Keywords

Biomedical sensors Tissue engineering Noninvasive monitoring Engineered tissue 

References

  1. 1.
    Abousleiman R. I., Sikavitsas V. I., Bioreactors for tissues of the musculoskeletal system, Adv. Exp. Med. Biol., 585: 243–259, 2006PubMedCrossRefGoogle Scholar
  2. 2.
    Abrantes M., Magone M. T., Boyd L. F., Schuck P., Adaptation of a surface plasmon resonance biosensor with microfluidics for use with small sample volumes and long contact times, Anal. Chem., 73(13): 2828–2835, 2001PubMedCrossRefGoogle Scholar
  3. 3.
    Ahmad R., Clymer B., Vikram D. S., Deng Y., Hirata H., Zweier J. L., Kuppusamy P., Enhanced resolution for EPR imaging by two-step deblurring, J. Magn. Reson., 184(2): 246–257, 2007PubMedCrossRefGoogle Scholar
  4. 4.
    Allen C. R., Giffin J. R., Harner C. D., Revision anterior cruciate ligament reconstruction, Ortho. Clin. N Am. 34(1):79–98, 2003CrossRefGoogle Scholar
  5. 5.
    Alleyne K. R., Galloway M. T., Management of osteochondral injuries of the knee, Clin. Sports Med. 20(2):343–364, 2001PubMedCrossRefGoogle Scholar
  6. 6.
    Amao Y., Probes and polymers for optical sensing of oxygen, Microchimica Acta, 143(1): 1–12, 2003CrossRefGoogle Scholar
  7. 7.
    Atala A., Bauer S. B., Soker S., Yoo J. J., Retik A. B., Tissue-engineered autologous bladders for patients needing cystoplasty, Lancet, 367(9518): 1215–1216, 2006CrossRefGoogle Scholar
  8. 8.
    Bagnaninchi P. O., Dikeakos M., Veres T., Tabrizian M., Complex permittivity measurement as a new noninvasive tool for monitoring in vitro tissue engineering and cell signature through the detection of cell proliferation, differentiation, and pretissue formation, IEEE Trans. Nanobiosci., 3(4): 243–250, 2004CrossRefGoogle Scholar
  9. 9.
    Bagnaninchi P. O., Dikeakos M., Veres T., Tabrizian M., Towards on-line monitoring of cell growth in microporous scaffolds: Utilization and interpretation of complex permittivity measurements, Biotechnol. Bioeng., 84(3): 343–350, 2003PubMedCrossRefGoogle Scholar
  10. 10.
    Bashir R., BioMEMS: state-of-the-art in detection, opportunities and prospects, J. Adv. Drug Delivery Rev., 56(11): 1565–1586, 2004CrossRefGoogle Scholar
  11. 11.
    Bhatia S. Cell and tissue based sensors, WTEC Workshop on Biosensing Research and Development in the United States, 2001Google Scholar
  12. 12.
    Bilgen B., Sucosky P., Neitzel G. P., Barabino G. A., Flow characterization of a wavy-walled bioreactor for cartilage tissue engineering, Biotechnol. Bioeng., 95(6): 1009–1022, 2006PubMedCrossRefGoogle Scholar
  13. 13.
    Burke C. S., A. Markey, R. I. Nooney, P. Byrne, and C. McDonagh. Development of an optical sensor probe for the detection of dissolved carbon dioxide, Sens. Actuators B, 119(1): 288–294, 2006CrossRefGoogle Scholar
  14. 14.
    Campbell A., Uttamchandani D., Optical dissolved oxygen lifetime sensor based on sol-gel immobilisation, IEE Proc. Sci. Meas. Technol., 151(4): 291–297, 2004CrossRefGoogle Scholar
  15. 15.
    Cao W., Duan Y., Optical fiber evanescent wave sensor for oxygen deficiency detection, Sens. Actuators B, 119(2): 363–369, 2006CrossRefGoogle Scholar
  16. 16.
    Chang-Yen D. A., Gale B. K., An integrated optical biochemical sensor fabricated using rapid-prototyping techniques, Lab. Chip., 3: 297–301, 2003PubMedCrossRefGoogle Scholar
  17. 17.
    Choi S., Park J. K., Microfluidic system for dielectrophoretic separation based on a trapezoidal electrode array, Lab. Chip., 5: 1161–1167, 2005PubMedCrossRefGoogle Scholar
  18. 18.
    Choong C. S., Hutmacher D. W., Triffitt J. T., Co-culture of bone marrow fibroblasts and endothelial cells on modified polycaprolactone substrates for enhanced potentials in bone tissue engineering, Tissue Eng., 12(9): 2521–2531, 2006PubMedCrossRefGoogle Scholar
  19. 19.
    Darling A., Shor L., Khalil S., Mondrinos M., Lelkes P., Guceri S., Sun W., Multi-material scaffolds for tissue engineering, Macromol. Symposia, 27(1): 345–356, 2005CrossRefGoogle Scholar
  20. 20.
    Deng Y., Pandian R. P., Ahmad R., Kuppusamy P., Zweier J. L., Application of magnetic field over-modulation for improved EPR linewidth measurements using probes with Lorentzian lineshape, J. Magn. Reson. 181(2): 254–261, 2006PubMedCrossRefGoogle Scholar
  21. 21.
    Dobson J., Cartmell S. H., Keramane A., El Haj A. J., Principles and design of a novel magnetic force mechanical conditioning bioreactor for tissue engineering, stem cell conditioning, and dynamic in vitro screening, IEEE Trans. Nanobiosci., 5(3):173–177, 2006CrossRefGoogle Scholar
  22. 22.
    Eaglstein W. H., Falanga V., Tissue engineering and the development of Apligraf, a human skin equivalent, Clin. Ther., 19(5):894–905, 1997PubMedCrossRefGoogle Scholar
  23. 23.
    Ellis J. S, Velayutham M., Velan S. S., Petersen F. E., Zweier L. J., Kuppusamy P., Spencer G. S. R., EPR oxygen mapping (EPROM) of engineered cartilage grown in a hollow-fiber bioreactor, Magn. Reson. Med. 46:819–826, 2001PubMedCrossRefGoogle Scholar
  24. 24.
    Ge X., Kostov Y., Rao G., High-stability non-invasive autoclavable naked optical CO2 sensor, Biosens. Bioelectr., 18(7): 857–865, 2003CrossRefGoogle Scholar
  25. 25.
    Griffith L. G., Emerging design principles in biomaterials and scaffolds for tissue engineering, Ann. NY Acad. Sci., 961: 83–95, 2002PubMedCrossRefGoogle Scholar
  26. 26.
    Griffith L. G., Swartz M. A., Capturing complex 3D tissue physiology in vitro, Nat. Rev. Mol. Cell. Biol., 7(3): 211–224, 2006PubMedCrossRefGoogle Scholar
  27. 27.
    Guarino R. D., Dike L. E., Haq T. A., Rowley J. A., Pitner J. B., Timmins M. R., Method for determining oxygen consumption rates of static cultures from microplate measurements of pericellular dissolved oxygen concentration, Biotechnol. Bioeng., 86(7): 775–787, 2004PubMedCrossRefGoogle Scholar
  28. 28.
    Gupta B. D., Dodeja H., Tomar A. K., Fibre-optic evanescent field absorption sensor based on a U-shaped probe, Optical Quant. Electron., 28(11):1629–1639, 1996CrossRefGoogle Scholar
  29. 29.
    Halaka F., Dielectrophoretic dynamic light-scattering (DDLS) spectroscopy, Proc. Natl. Acad. Sci. USA, 100(18):10164–10169, 2003PubMedCrossRefGoogle Scholar
  30. 30.
    Holden M. A., Kumar S., Castellana E., Beskok A., Cremer P., Generating fixed concentration arrays in a microfluidic device, Sens. Actuators B Chem., 92(1–2): 199–207, 2003CrossRefGoogle Scholar
  31. 31.
    Hong S., Ergezen E., Lec R., Barbee K. A., Real-time analysis of cell-surface adhesive interactions using thickness shear mode resonator, Biomaterials, 27(34): 5813–5820, 2006PubMedCrossRefGoogle Scholar
  32. 32.
    Janshoff A., Wegener J., Sieber M., Galla H. J., Double-mode impedance analysis of epithelial cell monolayers cultured on shear wave resonators, Eur. Biophys. J, 25(2): 93–103, 1996PubMedCrossRefGoogle Scholar
  33. 33.
    Jenkner M., Tartagni M., Hierlemann A., Thewes R., Cell based CMOS sensor and actuator arrays, IEEE J. Solid State Circuit. 39(12): 2431–2437, 2004CrossRefGoogle Scholar
  34. 34.
    Kellner K., Liebsch G., Klimant I., Wolfbeis O. S., Blunk T., Schulz M. B., Gopferich A., Determination of oxygen gradients in engineered tissue using a fluorescent sensor, Biotechnol. Bioeng., 80(1): 73–83, 2002PubMedCrossRefGoogle Scholar
  35. 35.
    Kermis H. R., Kostov Y., Harms P., Rao G., Dual excitation ratiometric fluorescent pH sensor for noninvasive bioprocess monitoring: development and application, Biotechnol. Prog., 18(5): 1047–1053, 2002PubMedCrossRefGoogle Scholar
  36. 36.
    Khoshnoodi J., Sjgmundsson K., Cartailler J., Bondar O., Sundaramoorthy M., Hudson B. G., Mechanism of chain selection in the assembly of collagen IV: a prominentrole for the α2 chain, J. Biol. Chem., 281(9): 6058–6069, 2006PubMedCrossRefGoogle Scholar
  37. 37.
    Knoll A., Scherer T., Poggendorf I., Lutkemeyer D., Lehmann J., Flexible automation of cell culture and tissue engineering tasks, Biotechnol. Progress, 20(6): 1825–1835, 2004CrossRefGoogle Scholar
  38. 38.
    Kohls O., Scheper T., Setup of a fiber optical oxygen multisensor-system and its applications in biotechnology, Sens. Actuators B, 70(1–3): 121–130, 2000CrossRefGoogle Scholar
  39. 39.
    Langer R., Tissue Engineering: a new field and its challenges, Sci. Am., 280: 86–89, 1999PubMedCrossRefGoogle Scholar
  40. 40.
    Laurencin C. T., El-Amin S. F., Ibim S. E., Willoughby D. A., Attawia M., Allcock H. R., Ambrosio A. A., A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration, J. Biomed. Mater. Res., 30(2): 133–138, 1996PubMedCrossRefGoogle Scholar
  41. 41.
    Lec, R. Acoustic wave biosensors: recent advances and applications. In: Proc. of the 2001 IEEE International Frequency Control Symposium, 2001, pp. 419–430Google Scholar
  42. 42.
    Lee H. L., Boccazzi P., Ram R. J., Sinskey A. J., Microbioreactor arrays with integrated mixers and fluid injectors for high-throughput experimentation with pH and dissolved oxygen control, Lab. Chip. 6(9): 1229–1235, 2006PubMedCrossRefGoogle Scholar
  43. 43.
    Liu, Y., and S. Wang. 3D inverted opal hydrogel scaffolds with oxygen sensing capability. Colloid Surf. B Biointerf. 58(1): 8–13, 2007CrossRefGoogle Scholar
  44. 44.
    Lorenzelli L., Margesin B., Martinoia S., Tedesco M. T., Valle M., Bioelectrochemical signal monitoring of in-vitro cultured cells by means of an automated microsystem based on solid state sensor-array, Biosens. Bioelectron., 18(5–6): 621–626, 2003PubMedCrossRefGoogle Scholar
  45. 45.
    Lu H. B., Campbell C. T., Castner D. G., Attachment of functionalized poly(ethylene glycol) films to gold surfaces, Langmuir, 16(4): 1711–1718, 2000CrossRefGoogle Scholar
  46. 46.
    Lung F. D. T., Chen C. H., Liou C. C., Chen H. Y., Surface plasmon resonance detection of interactions between peptide fragments of N-telopeptide and its monoclonal antibodies, J. Peptide Res., 63(4): 365–370, 2004CrossRefGoogle Scholar
  47. 47.
    Malda J., Woodfield T. B., Van der Vloodt F., Wilson C., Martens D. E., Tramper J., Van Blitterswijk C. A., Riesle J., The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs, Biomaterials, 25(26): 5773–5780, 2004PubMedCrossRefGoogle Scholar
  48. 48.
    Malins C., Glever H. G., Keyes T. E., Vos J. G., Dressick W. J., MacCraith B. D., Sol–gel immobilised ruthenium II polypyridyl complexes as chemical transducers for optical pH sensing, Sens. Actuators B, 67: 89–95, 2000CrossRefGoogle Scholar
  49. 49.
    McCulloch S., Uttamchandani D., Development of a fibre optic micro-optrode for intracellular pH measurements, IEEE Proc. OptoElectron, 144(3): 162–167, 1997CrossRefGoogle Scholar
  50. 50.
    McDonagh C., Lowe P., Mongey K., MacCraith B. D., Characterization of porosity and sensor response times of sol–gel derived thin film for oxygen sensor applications, J. Non-Crystal. Solid., 306(2): 138–148, 2002CrossRefGoogle Scholar
  51. 51.
    McIntire L. V., World technology panel report on tissue engineering, Annl. Biomed. Eng., 30(10): 1216–1220, 2002CrossRefGoogle Scholar
  52. 52.
    McShane M. J., Rastegar S., Pishko M., Cote G. L., Monte Carlo modeling for implantable fluorescent analyte sensors, IEEE Trans. Biomed. Eng., 47(5):624–632, 2000PubMedCrossRefGoogle Scholar
  53. 53.
    Mironov V., Visconti R. P., Markwald R. R., What is regenerative medicine? Emergence of applied stem cell and developmental biology, Expert Opin. Biol. Ther. 4(6): 773–781, 2004PubMedCrossRefGoogle Scholar
  54. 54.
    Munakata H., Takagaki K., Majima M., Endo M., Interaction between collagens and glycosaminoglycans investigated using a surface plasmon resonance biosensor, Glycobiology, 9(10): 1023–1027, 1999PubMedCrossRefGoogle Scholar
  55. 55.
    Nerem, R. Cell-based therapies: from basic biology to replacement, repair, and regeneration. Biomaterials 28(34):5074–5077, 2007PubMedCrossRefGoogle Scholar
  56. 56.
    O’Neal D., Meledeo A., Davis J. R., Ibey B. L., Gant V. A., Pishko M. V., Cote G. L., Oxygen sensor based on the fluorescence quenching of a ruthenium complex immobilized in a biocompatible poly(ethylene glycol) hydrogel, IEEE Sensor. J., 4(6): 728–734, 2004CrossRefGoogle Scholar
  57. 57.
    Okano T., Yamato M., Nishida K., Hayashida Y., Watanabe K., Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium, N. Engl. J. Med. 351: 1187–1196, 2004PubMedCrossRefGoogle Scholar
  58. 58.
    O’Keeffe G., MacCraith B. D., McEvoy A. K., McDonagh C. M., McGilp J. F., Development of a LED-based phase fluorimetric oxygen sensor using evanescent wave excitation of a sol–gel immobilized dye, Sens. Actuators B, 29(1): 226–230, 1995CrossRefGoogle Scholar
  59. 59.
    Petroua P. S., Moserb I., Jobst G., Microdevice with integrated dialysis probe and biosensor array for continuous multi-analyte monitoring, J. Biosens. Bioelectron., 18(5–6): 613–619, 2003CrossRefGoogle Scholar
  60. 60.
    Robson M. A. W., Rutured cruciate ligaments and their repair by operation, Ann. Surg., 37: 716–718, 1903PubMedGoogle Scholar
  61. 61.
    Rolfe P., Optical examination of cell culture in bioreactors creating simulated in vivo conditions, Proc. SPIE, 5630: 439–446, 2005CrossRefGoogle Scholar
  62. 62.
    Rolfe P., Optics in cell and tissue engineering, Proc. SPIE, 5771: 130–138, 2005CrossRefGoogle Scholar
  63. 63.
    Rolfe P., Sensing in tissue bioreactors, Meas. Sci. Technol, 17: 578–583, 2006CrossRefGoogle Scholar
  64. 64.
    Rosenzweig Z., Kopelman R., Analytical properties of miniaturized oxygen and glucose fiber optic sensors, Sens. Actuators B Chem., 36(1–3): 475–483, 1996CrossRefGoogle Scholar
  65. 65.
    Sachlos E., Czernuszka J. T., Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds, Eur. Cell Mater. 30(5): 29–39, 2003Google Scholar
  66. 66.
    Saim A. B., Cao Y., Weng Y., Chang C. N., Vacanti M. A., Vacanti C. A., Eavey R. D., Engineering autogenous cartilage in the shape of a helix using an injectable hydrogel scaffold, Laryngoscope, 110(10): 1694–1697, 2000PubMedCrossRefGoogle Scholar
  67. 67.
    Saltzman, M. Tissue Engineering: Engineering Principles for the Design of Replacement Organs and Tissues. USA: Oxford University Press, ISBN-10:019514130Google Scholar
  68. 68.
    Schwyer, M. G., J. A. Hilton, J. E. Munson, J. C. Andle, J. M. Hammond, and R. M. Lec. A novel monolithic piezoelectric sensor. In: Proc. of the 1997 IEEE International Frequency Control Symposium, Orlando, FLGoogle Scholar
  69. 69.
    Segawa H., Ohnishi E., Arai Y., Yoshida K., Sensitivity of fiber-optic carbon dioxide sensors utilizing indicator dye, Sens. Actuators B, 94(3): 276–281, 2003CrossRefGoogle Scholar
  70. 70.
    Shao X., Hutmacher D. W., Ho A. T., Goh J. C. H., Lee E., Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits , Biomaterials, 27(7): 1071–1080, 2006PubMedCrossRefGoogle Scholar
  71. 71.
    Shumaker-Parry J., Campbell C. T., Quantitative methods for spatially-resolved adsorption/desorption measurements in real time by SPR microscopy, Anal. Chem., 76(4): 907–917, 2004PubMedCrossRefGoogle Scholar
  72. 72.
    Soelberg S. D., Chinowsky T., Geiss G., Spinelli C. B., Stevens R., Near S., Kauffman P., Yee S., Furlong C. E., A portable surface plasmon resonance sensor system for real-time monitoring of small to large analytes, J. Ind. Microbiol. Biotechnol., 32(11–12): 669–674, 2005PubMedGoogle Scholar
  73. 73.
    Sun W., Yan Y., Lin F., Spector M., Biomanufacturing: a US–China National Science Foundation-sponsored workshop, Tissue Eng., 12(5): 169–1181, 2006CrossRefGoogle Scholar
  74. 74.
    Tan W., Shi Z. Y., Smith S., Birnbaum D., Kopelman R., Submicrometer intracellular chemical optical fiber sensors, Science, 258: 778–781, 1992PubMedCrossRefGoogle Scholar
  75. 75.
    Tang Y., Tehan E. C., Tao Z., Bright F. V., Sol–gel-derived sensor materials that yield linear calibration plots, high sensitivity, and long-term stability, Anal. Chem., 75(10): 2407–2413, 2003PubMedCrossRefGoogle Scholar
  76. 76.
    Velan S. S., Spencer R., Zweier J. L., Kuppusamy P., Electron paramagnetic resonance oxygen mapping (EPROM): Direct visualization of oxygen concentration in tissue, Magn. Reson. Med. 43: 804–809, 2000PubMedCrossRefGoogle Scholar
  77. 77.
    Walt, D. R. Optical biosensing. In: WTEC Workshop on Biosensing Research and Development in the United States, 2005Google Scholar
  78. 78.
    Wang W., Vadgama P., Oxygen microsensors for minimally invasive tissue monitoring, J. R. Soc. Interf., 1(1): 109–117, 2004CrossRefGoogle Scholar
  79. 79.
    Wendt D., Stroebel S., Jakob M., John G. T., Martin I., Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions, Biorheology, 43(3–4): 481–488, 2006PubMedGoogle Scholar
  80. 80.
    Xu X., Smith S., Urban J., Cui Z., An in line non-invasive optical system to monitor pH in cell and tissue culture, Med. Eng. Phys., 28(5): 468–474, 2006PubMedCrossRefGoogle Scholar
  81. 81.
    Yang Y., Yiu H. H., El Haj A. J., On-line fluorescent monitoring of the degradation of polymeric scaffolds for tissue engineering, Analyst, 130(11): 1502–1506, 2005PubMedCrossRefGoogle Scholar
  82. 82.
    Yeh T. S., Chub C. S., Lo Y. L., Highly sensitive optical fiber oxygen sensor using Pt(II) complex embedded in sol–gel matrices, Sens. Actuators B, 119(2): 701–707, 2006CrossRefGoogle Scholar
  83. 83.
    Yen-Chih H., Khait L., Birla R. K., Contractile three-dimensional bioengineered heart muscle for myocardial regeneration, J. Biomed. Mater. Res. A, 80A(3): 719–731, 2006Google Scholar
  84. 84.
    Zhang S., Tanaka S., Yappa A., Wickramasinghe B. D., Rolfe P., Fibre–optical sensor based on fluorescent indicator for monitoring physiological pH values, Med. Biol. Eng. Comput., 33(2): 152–156, 1995PubMedCrossRefGoogle Scholar
  85. 85.
    Zhang Y., Wilson G. S., In vitro and in vivo evaluation of oxygen effects on a glucose oxidase based implantable glucose sensor, Anal. Chim. Acta., 281: 513–520, 1993CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2007

Authors and Affiliations

  1. 1.School of Industrial EngineeringUniversity of OklahomaNormanUSA
  2. 2.School of BioengineeringUniversity of OklahomaNormanUSA

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