Abstract

A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate. Feasibility of the glucose sensor was verified by both in vitro and in vivo experiments.

© 2014 Optical Society of America

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  1. J. D. Newman and A. P. F. Turner, “Home blood glucose biosensors: a commercial perspective,” Biosens. Bioelectron. 20(12), 2435–2453 (2005).
    [Crossref] [PubMed]
  2. J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
    [Crossref]
  3. M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
    [Crossref] [PubMed]
  4. M. M. Ahmadi and G. A. Jullien, “A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring,” IEEE Trans. Biomed. Circuits Syst. 3(3), 169–180 (2009).
    [Crossref] [PubMed]
  5. Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
    [Crossref]
  6. M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
    [Crossref] [PubMed]
  7. T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
    [Crossref] [PubMed]
  8. H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
    [Crossref] [PubMed]
  9. Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
    [Crossref] [PubMed]
  10. T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
    [Crossref] [PubMed]
  11. T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
    [Crossref] [PubMed]
  12. M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
    [Crossref]
  13. E. R. Fossum, “CMOS image sensors: electronic camera-on-a-chip,” IEEE Trans. Electron. Dev. 44(10), 1689–1698 (1997).
    [Crossref]
  14. T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
    [Crossref]
  15. P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
    [Crossref] [PubMed]

2014 (2)

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

2012 (2)

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

2011 (2)

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

2010 (2)

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

2009 (1)

M. M. Ahmadi and G. A. Jullien, “A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring,” IEEE Trans. Biomed. Circuits Syst. 3(3), 169–180 (2009).
[Crossref] [PubMed]

2007 (1)

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

2005 (1)

J. D. Newman and A. P. F. Turner, “Home blood glucose biosensors: a commercial perspective,” Biosens. Bioelectron. 20(12), 2435–2453 (2005).
[Crossref] [PubMed]

2004 (1)

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

2002 (1)

J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
[Crossref]

1997 (1)

E. R. Fossum, “CMOS image sensors: electronic camera-on-a-chip,” IEEE Trans. Electron. Dev. 44(10), 1689–1698 (1997).
[Crossref]

1994 (1)

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Ahmadi, M. M.

M. M. Ahmadi and G. A. Jullien, “A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring,” IEEE Trans. Biomed. Circuits Syst. 3(3), 169–180 (2009).
[Crossref] [PubMed]

Akiyoshi, K.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Arakawa, T.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Bondia, J.

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

Chu, M. X.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Fanelli, C. G.

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

Fossum, E. R.

E. R. Fossum, “CMOS image sensors: electronic camera-on-a-chip,” IEEE Trans. Electron. Dev. 44(10), 1689–1698 (1997).
[Crossref]

Gilligan, B. J.

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Haruta, M.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Heo, Y. J.

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Holody, M. Z.

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Ishikawa, Y.

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Iwasaki, Y.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Jullien, G. A.

M. M. Ahmadi and G. A. Jullien, “A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring,” IEEE Trans. Biomed. Circuits Syst. 3(3), 169–180 (2009).
[Crossref] [PubMed]

Kagawa, K.

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Kawanishi, T.

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Kitsumoto, C.

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

Kobayashi, T.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Kudo, H.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Lesho, M.

J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
[Crossref]

Liao, Y.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Lingley, A.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Masuda, H.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Matsunaga, Y.

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Matsuo, M.

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Member, S.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Mitsubayashi, K.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Miyajima, K.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Mochizuki, M.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Motoyama, M.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Newman, J. D.

J. D. Newman and A. P. F. Turner, “Home blood glucose biosensors: a commercial perspective,” Biosens. Bioelectron. 20(12), 2435–2453 (2005).
[Crossref] [PubMed]

Noda, T.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Nunoshita, M.

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Ohta, J.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Ohta, Y.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Okitsu, T.

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Otis, B. P.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Parviz, B.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Reining, W. N.

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Rhodes, R. K.

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Romey, M. A.

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Rossetti, P.

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

Sano, K.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Sasagawa, K.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Sawada, S.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Shibata, H.

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Shinkai, S.

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Shiosaka, S.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Shults, M. C.

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Sunaga, Y.

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

Takahashi, D.

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

Takehara, H.

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

Takeuchi, S.

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Tamada, J. A.

J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
[Crossref]

Tamura, H.

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

Tanaka, K.

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Tierney, M. J.

J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
[Crossref]

Tokuda, T.

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Turner, A. P. F.

J. D. Newman and A. P. F. Turner, “Home blood glucose biosensors: a commercial perspective,” Biosens. Bioelectron. 20(12), 2435–2453 (2005).
[Crossref] [PubMed]

Updike, S. J.

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

Vehí, J.

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

Yao, H.

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

Zhu, P. C.

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Biosens. Bioelectron. (3)

J. D. Newman and A. P. F. Turner, “Home blood glucose biosensors: a commercial perspective,” Biosens. Bioelectron. 20(12), 2435–2453 (2005).
[Crossref] [PubMed]

T. Kobayashi, M. Motoyama, H. Masuda, Y. Ohta, M. Haruta, T. Noda, K. Sasagawa, T. Tokuda, H. Tamura, Y. Ishikawa, S. Shiosaka, and J. Ohta, “Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex,” Biosens. Bioelectron. 38(1), 321–330 (2012).
[Crossref] [PubMed]

T. Kobayashi, H. Masuda, C. Kitsumoto, M. Haruta, M. Motoyama, Y. Ohta, T. Noda, K. Sasagawa, T. Tokuda, S. Shiosaka, and J. Ohta, “Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system,” Biosens. Bioelectron. 53, 31–36 (2014).
[Crossref] [PubMed]

IEEE J. Solid-State Circuits (1)

Y. Liao, H. Yao, A. Lingley, B. Parviz, S. Member, and B. P. Otis, “A 3-uW CMOS glucose sensor for wireless contact-lens tear glucose monitoring,” IEEE J. Solid-State Circuits 47(1), 335–344 (2012).
[Crossref]

IEEE Spectr. (1)

J. A. Tamada, M. Lesho, and M. J. Tierney, “Keeping watch on glucose,” IEEE Spectr. 39(4), 52–57 (2002).
[Crossref]

IEEE Trans. Biomed. Circuits Syst. (1)

M. M. Ahmadi and G. A. Jullien, “A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring,” IEEE Trans. Biomed. Circuits Syst. 3(3), 169–180 (2009).
[Crossref] [PubMed]

IEEE Trans. Biomed. Eng. (1)

M. C. Shults, R. K. Rhodes, S. J. Updike, B. J. Gilligan, and W. N. Reining, “A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors,” IEEE Trans. Biomed. Eng. 41(10), 937–942 (1994).
[Crossref] [PubMed]

IEEE Trans. Electron. Dev. (1)

E. R. Fossum, “CMOS image sensors: electronic camera-on-a-chip,” IEEE Trans. Electron. Dev. 44(10), 1689–1698 (1997).
[Crossref]

J. Fluoresc. (1)

T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody, and S. Shinkai, “A Study of Boronic Acid Based Fluorescent Glucose Sensors,” J. Fluoresc. 14(5), 499–512 (2004).
[Crossref] [PubMed]

Jpn. J. Appl. Phys. (1)

M. Haruta, C. Kitsumoto, Y. Sunaga, H. Takehara, T. Noda, K. Sasagawa, T. Tokuda, and J. Ohta, “An implantable CMOS device for blood-flow imaging during experiments on freely moving rats,” Jpn. J. Appl. Phys. 53(4S), 04EL05 (2014).
[Crossref]

Proc. Natl. Acad. Sci. U.S.A. (2)

H. Shibata, Y. J. Heo, T. Okitsu, Y. Matsunaga, T. Kawanishi, and S. Takeuchi, “Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring,” Proc. Natl. Acad. Sci. U.S.A. 107(42), 17894–17898 (2010).
[Crossref] [PubMed]

Y. J. Heo, H. Shibata, T. Okitsu, T. Kawanishi, and S. Takeuchi, “Long-term in vivo glucose monitoring using fluorescent hydrogel fibers,” Proc. Natl. Acad. Sci. U.S.A. 108(33), 13399–13403 (2011).
[Crossref] [PubMed]

Sens. Actuators A Phys. (1)

T. Tokuda, K. Tanaka, M. Matsuo, K. Kagawa, M. Nunoshita, and J. Ohta, “Optical and electrochemical dual-image CMOS sensor for on-chip biomolecular sensing applications,” Sens. Actuators A Phys. 135(2), 315–322 (2007).
[Crossref]

Sensors (Basel) (1)

P. Rossetti, J. Bondia, J. Vehí, and C. G. Fanelli, “Estimating plasma glucose from interstitial glucose: the issue of calibration algorithms in commercial continuous glucose monitoring devices,” Sensors (Basel) 10(12), 10936–10952 (2010).
[Crossref] [PubMed]

Talanta (1)

M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, and K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment,” Talanta 83(3), 960–965 (2011).
[Crossref] [PubMed]

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Figures (9)

Fig. 1
Fig. 1 Concept of the CMOS-based implantable glucose-sensing system using glucose-responsive fluorescent hydrogel.
Fig. 2
Fig. 2 (a) Layout, (b) block diagram, and (c) schematic of the implantable CMOS image sensor. In (c), ΦRST, ΦX_SEL and ΦY_SEL are generated by the horizontal and the vertical scanners, and VRST and Vbn are generated by the internal bias circuitry in (b).
Fig. 3
Fig. 3 Structure of (a) the core hardware, and the devices for (b) basic in vitro, (c) semi-chronic in vitro, and (d) in vivo functional verification.
Fig. 4
Fig. 4 Images taken during the in vitro glucose measurement experiment. Images were taken in W/B, and shown in pseudo-color. Line profiles are also shown. A 30 × 90 version of the image sensor was used.
Fig. 5
Fig. 5 Sensor output levels for pixels 1–5 (see Fig. 4) as a function of glucose concentration. The LEDs were operated with 1 mA.
Fig. 6
Fig. 6 Typical glucose-monitoring trace obtained in the semi-chronic in vitro experiment.
Fig. 7
Fig. 7 (a) Sensitivity curves for glucose-monitoring trials in the semi-chronic in vitro experiments, and (b) sensitivity changes due to operation and storage in saline at 36°C.
Fig. 8
Fig. 8 (a) The rat's ear with the implanted glucose sensor, and (b) experimental procedure.
Fig. 9
Fig. 9 Change in the glucose concentration in the interstitial fluid as measured by the proposed implantable glucose sensor and an SMBG device. The two glucose levels are scaled to have the same swing.

Tables (1)

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Table 1 Specifications of the CMOS image sensor

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