Abstract

Abstract

A digital light modulation microscope (DLMM) that utilizes a digital micromirror device (DMD) on an epifluorescence microscope has been developed to modulate excitation light in spatial and temporal domains for phosphorescence lifetime detection. Local O2 concentration can be inferred through the detected lifetime around an O2-quenching phosphorescent porphyrin microsensor. Combined with microsensor arrays, the DLMM can sequentially address light to each microsensor element to construct a discrete lifetime image or O2 distribution. In contrast to conventional phosphorescence lifetime imaging, the new method eliminates the need for a pulsed light source and a time-gated camera. To demonstrate O2 sensing with lab-on-a-chip devices, an array of 150-µm-diameter micro-wells coated with phosphorescent porphyrin were observed. The locations of the sensor elements were automatically identified though image analysis. The goal of this platform is to measure the O2 consumption of individual cells trapped in the microwells.

© 2007 Optical Society of America

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    [Crossref]
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  5. S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).
  6. C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).
  7. P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
    [Crossref]
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    [Crossref] [PubMed]
  9. Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
    [Crossref]
  10. V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
    [Crossref] [PubMed]
  11. T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt.  42, 4119–4124 (2003).
    [Crossref] [PubMed]
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  13. P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
    [Crossref]
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  15. S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.
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    [Crossref]
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    [Crossref]
  18. T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).
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  20. R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng.  31, 1084–1096 (2003).
    [PubMed]
  21. G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
    [Crossref]
  22. M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
    [Crossref] [PubMed]
  23. S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.
  24. R. M. Haralick and L. G. Shapiro, “Computer and robot vision”. Reading, Mass.: Addison-Wesley Pub. Co, (1992).
  25. G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
    [Crossref]

2006 (2)

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
[Crossref] [PubMed]

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

2003 (2)

M. E. Lidstrom and D. R. Meldrum, “Life-on-a-chip,” Nat. Rev. Microbiol.  1, 158–164 (2003).
[Crossref]

T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt.  42, 4119–4124 (2003).
[Crossref] [PubMed]

2001 (1)

L. J. Hornbeck, “The DMD (TM) projection display chip: A MEMS-based technology,” Mrs. Bull.  26, 325–327 (2001).
[Crossref]

2000 (3)

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

1999 (1)

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

1998 (2)

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
[Crossref]

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

1996 (1)

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

1995 (1)

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

1993 (1)

D. B. Papkovsky, “Luminescent Porphyrins as Probes for Optical (Bio)Sensors,” Sens. Actuators, B-Chemical 11, 293–300 (1993).
[Crossref]

Anderson, J.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Anderson, J. B.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Bansal, V.

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
[Crossref] [PubMed]

Blair, N. P.

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

Botvinick, E. L.

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

Burgess, L.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Burgess, L. W.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Cha, S.

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

Chao, S.-H.

S.-H. Chao, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Oxygen concentration measurement with a phosphorescence lifetime based micro-sensor array using a digital light modulation microscope,” Proceedings of SPIE of Biomedical Optics and Imaging, 2006 (San Jose, CA), 6088, 60880S.

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

Chen, S. Pang

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

Dlugan, A.

C. MacAulay and A. Dlugan, “Use of digital micro mirror devices in quantitative microscopy,” in Optical Investigations of Cells In Vitro and In Vivo, Jan 25–28 1998 (The International Society for Optical Engineering, San Jose, CA), 201–206.

Dlugan, A. L. P.

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

Dragavon, J.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Dragavon, J. M.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Fainman, Y.

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

Frank, B.

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

Fukano, T.

T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt.  42, 4119–4124 (2003).
[Crossref] [PubMed]

Gales, S. A.

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

Gemkow, M. J.

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

Gruber, W.

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

Hanley, Q. S.

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
[Crossref]

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Haralick, R. M.

R. M. Haralick and L. G. Shapiro, “Computer and robot vision”. Reading, Mass.: Addison-Wesley Pub. Co, (1992).

Holl, M. R.

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

S.-H. Chao, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Oxygen concentration measurement with a phosphorescence lifetime based micro-sensor array using a digital light modulation microscope,” Proceedings of SPIE of Biomedical Optics and Imaging, 2006 (San Jose, CA), 6088, 60880S.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Holst, G.

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

Hornbeck, L. J.

L. J. Hornbeck, “The DMD (TM) projection display chip: A MEMS-based technology,” Mrs. Bull.  26, 325–327 (2001).
[Crossref]

Jen, A.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Jovin, D. Arndt

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

Jovin, T. M.

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
[Crossref]

Karlsgodt, B.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Kight, A. C.

R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng.  31, 1084–1096 (2003).
[PubMed]

Klimant, I.

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

Kolle, C.

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

Krause, A. W.

M. Liang, R. L. Stehr, and A. W. Krause, “Confocal microscope system that uses a binary spatial light modulator,” in Proceedings of the 1997 Conference on Lasers and Electro-Optics, CLEO, May 18–23 1997 (Optical Society of America, Washington DC, 1997), p. 154.

Lane, P. M.

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

Liang, M.

M. Liang, R. L. Stehr, and A. W. Krause, “Confocal microscope system that uses a binary spatial light modulator,” in Proceedings of the 1997 Conference on Lasers and Electro-Optics, CLEO, May 18–23 1997 (Optical Society of America, Washington DC, 1997), p. 154.

Lidstrom, M.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Lidstrom, M. E.

M. E. Lidstrom and D. R. Meldrum, “Life-on-a-chip,” Nat. Rev. Microbiol.  1, 158–164 (2003).
[Crossref]

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Liebsch, G.

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

Lijun, Z.

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

Lin, P. C.

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

MacAulay, C.

C. MacAulay and A. Dlugan, “Use of digital micro mirror devices in quantitative microscopy,” in Optical Investigations of Cells In Vitro and In Vivo, Jan 25–28 1998 (The International Society for Optical Engineering, San Jose, CA), 201–206.

MacAulay, C. E.

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

McQuaide, S. C.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

S.-H. Chao, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Oxygen concentration measurement with a phosphorescence lifetime based micro-sensor array using a digital light modulation microscope,” Proceedings of SPIE of Biomedical Optics and Imaging, 2006 (San Jose, CA), 6088, 60880S.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

Meldrum, D. R.

M. E. Lidstrom and D. R. Meldrum, “Life-on-a-chip,” Nat. Rev. Microbiol.  1, 158–164 (2003).
[Crossref]

S.-H. Chao, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Oxygen concentration measurement with a phosphorescence lifetime based micro-sensor array using a digital light modulation microscope,” Proceedings of SPIE of Biomedical Optics and Imaging, 2006 (San Jose, CA), 6088, 60880S.

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Meldrum, R. D.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Miyawaki, A.

T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt.  42, 4119–4124 (2003).
[Crossref] [PubMed]

Molter, T.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Molter, T. W.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Mori, M.

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

Papkovsky, D. B.

D. B. Papkovsky, “Luminescent Porphyrins as Probes for Optical (Bio)Sensors,” Sens. Actuators, B-Chemical 11, 293–300 (1993).
[Crossref]

Patel, S.

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
[Crossref] [PubMed]

Reininger, F.

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

Ren, T. T. H.

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

Richards-Kortum, R.

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

Saggau, P.

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
[Crossref] [PubMed]

Shahidi, M.

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

Shakoor, A.

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

Shapiro, L. G.

R. M. Haralick and L. G. Shapiro, “Computer and robot vision”. Reading, Mass.: Addison-Wesley Pub. Co, (1992).

Shonat, R. D.

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng.  31, 1084–1096 (2003).
[PubMed]

Stehr, R. L.

M. Liang, R. L. Stehr, and A. W. Krause, “Confocal microscope system that uses a binary spatial light modulator,” in Proceedings of the 1997 Conference on Lasers and Electro-Optics, CLEO, May 18–23 1997 (Optical Society of America, Washington DC, 1997), p. 154.

Strovas, T.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

Sun, P.-C.

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

Sungdo, C.

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

Trettnak, W.

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

Verbeek, P. W.

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Verveer, P. J.

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
[Crossref]

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Vliet, L. J. Van

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Wolfbeis, O. S.

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

Young, A. C.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

Zhu, L.

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

Ann. Biomed. Eng (1)

R. D. Shonat and A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng.  31, 1084–1096 (2003).
[PubMed]

Appl. Opt (1)

T. Fukano and A. Miyawaki, “Whole-field fluorescence microscope with digital micromirror device: imaging of biological samples,” Appl. Opt.  42, 4119–4124 (2003).
[Crossref] [PubMed]

Appl. Spectrosc (3)

Q. S. Hanley, P. J. Verveer, and T. M. Jovin, “Optical sectioning fluorescence spectroscopy in a programmable array microscope,” Appl. Spectrosc.  52, 783–789 (1998).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

G. Liebsch, I. Klimant, B. Frank, G. Holst, and O. S. Wolfbeis, “Luminescence lifetime imaging of oxygen, pH, and carbon dioxide,” Appl. Spectrosc.  54, 548–559 (2000).
[Crossref]

Curr. Eye. Res (1)

M. Shahidi, A. Shakoor, N. P. Blair, M. Mori, and R. D. Shonat, “A method for chorioretinal oxygen tension measurement,” Curr. Eye. Res.  31, 357–366 (2006).
[Crossref] [PubMed]

J. Biomed. Opt (1)

V. Bansal, S. Patel, and P. Saggau, “High-speed addressable confocal microscopy for functional imaging of cellular activity,” J. Biomed. Opt.  11, 34003–34011 (2006).
[Crossref] [PubMed]

J. Microsc (1)

Q. S. Hanley, P. J. Verveer, M. J. Gemkow, D. Arndt Jovin, and T. M. Jovin, “An optical sectioning programmable array microscope implemented with a digital micromirror device,” J. Microsc.  196, 317–331 (1999).
[Crossref] [PubMed]

J. Microsc. (1)

P. J. Verveer, Q. S. Hanley, P. W. Verbeek, L. J. Van Vliet, and T. M. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Med. Biol. Eng. Comput (1)

F. Reininger, C. Kolle, W. Gruber, and W. Trettnak, “Current progress in O2 measurement by luminescence quenching,” Med. Biol. Eng. Comput.  34, 113–114 (1996).

Mrs. Bull (1)

L. J. Hornbeck, “The DMD (TM) projection display chip: A MEMS-based technology,” Mrs. Bull.  26, 325–327 (2001).
[Crossref]

Nat. Rev. Microbiol (1)

M. E. Lidstrom and D. R. Meldrum, “Life-on-a-chip,” Nat. Rev. Microbiol.  1, 158–164 (2003).
[Crossref]

Opt. Lett (1)

P. M. Lane, A. L. P. Dlugan, R. Richards-Kortum, and C. E. MacAulay, “Fiber-optic confocal microscopy using a spatial light modulator,” Opt. Lett.  25, 1780–1782 (2000).
[Crossref]

Sens. Actuators B (1)

W. Trettnak, W. Gruber, F. Reininger, and I. Klimant, “Recent progress in optical oxygen sensor instrumentation,” Sens. Actuators B, 1–3 (1995).

Sens. Actuators, B-Chemical (1)

D. B. Papkovsky, “Luminescent Porphyrins as Probes for Optical (Bio)Sensors,” Sens. Actuators, B-Chemical 11, 293–300 (1993).
[Crossref]

Other (10)

T. W. Molter, M. R. Holl, J. M. Dragavon, S. C. McQuaide, J. B. Anderson, A. C. Young, L. W. Burgess, M. E. Lidstrom, and D. R. Meldrum, “A new approach for measuring single cell oxygen consumption rates,” IEEE T. Automat. Sci. Eng. (to appear).

“DMD discovery kit brochure,” in Productivity systems Inc.(2002).

S.-H. Chao, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Oxygen concentration measurement with a phosphorescence lifetime based micro-sensor array using a digital light modulation microscope,” Proceedings of SPIE of Biomedical Optics and Imaging, 2006 (San Jose, CA), 6088, 60880S.

S. C. McQuaide, M. R. Holl, L. Burgess, T. Molter, J. Dragavon, A. C. Young, T. Strovas, J. Anderson, A. Jen, B. Karlsgodt, M. Lidstrom, and R. D. Meldrum, “A Living Cell Array (LCA) for Multiparameter Cell Metabolism Studies,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 971–976.

C. MacAulay and A. Dlugan, “Use of digital micro mirror devices in quantitative microscopy,” in Optical Investigations of Cells In Vitro and In Vivo, Jan 25–28 1998 (The International Society for Optical Engineering, San Jose, CA), 201–206.

M. Liang, R. L. Stehr, and A. W. Krause, “Confocal microscope system that uses a binary spatial light modulator,” in Proceedings of the 1997 Conference on Lasers and Electro-Optics, CLEO, May 18–23 1997 (Optical Society of America, Washington DC, 1997), p. 154.

S. Cha, P. C. Lin, L. Zhu, E. L. Botvinick, P.-C. Sun, and Y. Fainman, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of SPIE of the Three-Dimensional Image Capture and Applications II, Jan 25-Jan 26 1999 3640, 246–253 (1999).

C. Sungdo, P. C. Lin, Z. Lijun, E. L. Botvinick, and S. Pang Chen, “3D profilometry using a dynamically configurable confocal microscope,” Proceedings of the SPIE The International Society for Optical, for-Optical (1999).

S.-H. Chao, T. T. H. Ren, S. A. Gales, M. R. Holl, S. C. McQuaide, and D. R. Meldrum, “Automated digital light modulation microscope (DLMM) for living cell array analysis: Pattern recognition and spatial alignment,” in IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (Pisa, Italy, 2006), 977–981.

R. M. Haralick and L. G. Shapiro, “Computer and robot vision”. Reading, Mass.: Addison-Wesley Pub. Co, (1992).

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Figures (7)

Fig. 1.
Fig. 1.

The microfabricated living cell array (LCA) with microwells etched on a glass substrate, where each well works as a cell trap with ring-shaped O2-sensitive phosphorescent material.

Fig. 2.
Fig. 2.

The schematic of the digital light modulation microscope (DLMM).

Fig. 3.
Fig. 3.

Images of two 150-µm diameter, ring-shaped phosphorescent patches imaged by the DLMM. The inserts on the lower-left of all images indicate the light pattern in the DMD (white areas represent switched-on micro-mirrors).

Fig. 4.
Fig. 4.

(a) The relationship of the coordinate system of the CCD camera to that of the DMD. (b-c) Calibration of the coordinate systems using a user interface that processes images from the CCD camera: (b) a DMD generated a horizontal line for calculating the rotation angle between two coordinate systems. (c) DMD generated squares for calculating the magnification between the two coordinate systems.

Fig. 5.
Fig. 5.

The procedure and demonstrated results of micro-well identification: a) raw fluorescence image of five micro-wells, b) thresholding the raw image into a binary image, c) morphological processing to remove undesired artifacts, and d) estimating the geometrical parameters (unit: pixel).

Fig. 6.
Fig. 6.

The phosphorescence decay curves of the detected O2 sensor patch (solid lines) and fit curves (dashed lines). (a) ambient conditions (~21% O2); (b) depleted O2 conditions (~0% O2).

Fig. 7.
Fig. 7.

(a) Images of five wells with O2 sensing phosphorescent rings. (b) The measured phosphorescence decay curves of the O2 sensors and the inferred decay time τ ^ .

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

I em ( t ) I ¯ em = e t τ ,
τ 0 τ = 1 + K sv [ O 2 ] ,
[ x y ] = M [ cos θ sin θ sin θ cos θ ] [ x ¯ x ¯ 0 y ¯ y ¯ 0 ]

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