Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

An implantable microfluidic device for self-monitoring of intraocular pressure

Abstract

Glaucoma is the second most common cause of blindness in the world. It is a multifactorial disease with several risk factors, of which intraocular pressure (IOP) is a primary contributing factor. IOP measurements are used for glaucoma diagnosis and patient monitoring. IOP has wide diurnal fluctuation and is dependent on body posture, so the occasional measurements done by the eye care expert in the clinic can be misleading. Here we show that microfluidic principles can be used to develop an implantable sensor that has a limit of detection of 1 mm Hg, high sensitivity and excellent reproducibility. This device has a simple optical interface that enables IOP to be read with a smartphone camera. This sensor, with its ease of fabrication and simple design, as well as its allowance for IOP home monitoring, offers a promising approach for better care of patients with glaucoma.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: IOP measurement system embedded in an intraocular lens.
Figure 2: Microfluidic intraocular sensor.
Figure 3: IOP sensor implanted in a porcine eye.
Figure 4: IOP readout with a smartphone.

References

  1. Quigley, H.A. & Broman, A.T. The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262–267 (2006).

    Article  CAS  Google Scholar 

  2. Quigley, H.A. Number of people with glaucoma worldwide. Br. J. Ophthalmol. 80, 389–393 (1996).

    Article  CAS  Google Scholar 

  3. Pascolini, D. & Mariotti, S.P. Global estimates of visual impairment: 2010. Br. J. Ophthalmol. 96, 614–618 (2012).

    Article  Google Scholar 

  4. Thylefors, B. & Négrel, A.D. The global impact of glaucoma. Bull. World Health Organ. 72, 323–326 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Klein, B.E., Klein, R. & Linton, K.L. Intraocular pressure in an American community. The Beaver Dam Eye Study. Invest. Ophthalmol. Vis. Sci. 33, 2224–2228 (1992).

    CAS  PubMed  Google Scholar 

  6. Coleman, A.L. Advances in glaucoma treatment and management: surgery. Invest. Ophthalmol. Vis. Sci. 53, 2491–2494 (2012).

    Article  Google Scholar 

  7. Hughes, E., Spry, P. & Diamond, J. 24-hour monitoring of intraocular pressure in glaucoma management: a retrospective review. J. Glaucoma 12, 232–236 (2003).

    Article  Google Scholar 

  8. Becker, B. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J. Glaucoma 9, 487–488 (2000).

    Article  CAS  Google Scholar 

  9. Kiuchi, T., Motoyama, Y. & Oshika, T. Postural response of intraocular pressure and visual field damage in patients with untreated normal-tension glaucoma. J. Glaucoma 19, 191–193 (2010).

    Article  Google Scholar 

  10. Kwon, T.H., Ghaboussi, J., Pecknold, D.A. & Hashash, Y.M.A. Effect of cornea material stiffness on measured intraocular pressure. J. Biomech. 41, 1707–1713 (2008).

    Article  CAS  Google Scholar 

  11. Doughty, M.J. & Jonuscheit, S. Effect of central corneal thickness on Goldmann applanation tonometry measures - a different result with different pachymeters. Graefes Arch. Clin. Exp. Ophthalmol. 245, 1603–1610 (2007).

    Article  Google Scholar 

  12. Liu, J.H.K. & Weinreb, R.N. Monitoring intraocular pressure for 24 h. Br. J. Ophthalmol. 95, 599–600 (2011).

    Article  Google Scholar 

  13. Rizq, R.N., Choi, W.H., Eilers, D., Wright, M.M. & Ziaie, B. Intraocular pressure measurement at the choroid surface: a feasibility study with implications for implantable microsystems. Br. J. Ophthalmol. 85, 868–871 (2001).

    Article  CAS  Google Scholar 

  14. Cherrier, M., Erichsen, I. & Krey, S. Characterization of intraocular lenses: a comparison of different measurement methods. Proc. SPIE 7556, 75560W (2010).

    Article  Google Scholar 

  15. Fry, L.L. Another possible cause of forceps-induced scratching of a foldable acrylic intraocular lens. Arch. Ophthalmol. 115, 823 (1997).

    Article  CAS  Google Scholar 

  16. Harsum, S., Mann, S., Clatworthy, I., Lewin, J. & Little, B. An investigation of intraocular lens damage and foreign bodies using an injectable hydrophilic acrylic lens implant. Eye (Lond.) 24, 152–157 (2010).

    Article  CAS  Google Scholar 

  17. Unger, M.A., Chou, H.P., Thorsen, T., Scherer, A. & Quake, S.R. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288, 113–116 (2000).

    Article  CAS  Google Scholar 

  18. Elman, N.M. & Upadhyay, U.M. Medical applications of implantable drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems). Curr. Pharm. Biotechnol. 11, 398–403 (2010).

    Article  CAS  Google Scholar 

  19. The Agis Investigators. The Advanced Glaucoma Intervention Study: 8. Risk of cataract formation after trabeculectomy. Arch. Ophthalmol. 119, 1771–1779 (2001).

  20. Hylton, C. et al. Cataract after glaucoma filtration surgery. Am. J. Ophthalmol. 135, 231–232 (2003).

    Article  Google Scholar 

  21. Meyer, M.A., Savitt, M.L. & Kopitas, E. The effect of phacoemulsification on aqueous outflow facility. Ophthalmology 104, 1221–1227 (1997).

    Article  CAS  Google Scholar 

  22. Bömer, T.G., Lagrèze, W.D. & Funk, J. Intraocular pressure rise after phacoemulsification with posterior chamber lens implantation: effect of prophylactic medication, wound closure, and surgeon's experience. Br. J. Ophthalmol. 79, 809–813 (1995).

    Article  Google Scholar 

  23. Harvey, P., Woodward, B., Datta, S. & Mulvaney, D. Data acquisition in a wireless diabetic and cardiac monitoring system. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 3154–3157 (2011).

    PubMed  Google Scholar 

  24. Logan, A.G. et al. Effect of home blood pressure telemonitoring with self-care support on uncontrolled systolic hypertension in diabetics. Hypertension 60, 51–57 (2012).

    Article  CAS  Google Scholar 

  25. Wagenaar, R.C. et al. Continuous monitoring of functional activities using wearable, wireless gyroscope and accelerometer technology. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 4844–4847 (2011).

    PubMed  Google Scholar 

  26. Gandhi, P.D., Gurses-Ozden, R., Liebmann, J.M. & Ritch, R. Attempted eyelid closure affects intraocular pressure measurement. Am. J. Ophthalmol. 131, 417–420 (2001).

    Article  CAS  Google Scholar 

  27. McLaren, J.W., Brubaker, R.F. & FitzSimon, J.S. Continuous measurement of intraocular pressure in rabbits by telemetry. Invest. Ophthalmol. Vis. Sci. 37, 966–975 (1996).

    CAS  PubMed  Google Scholar 

  28. Kakaday, T., Hewitt, A.W., Voelcker, N.H., Li, J.S.J. & Craig, J.E. Advances in telemetric continuous intraocular pressure assessment. Br. J. Ophthalmol. 93, 992–996 (2009).

    Article  CAS  Google Scholar 

  29. Stangel, K. et al. A programmable intraocular CMOS pressure sensor system implant. IEEE J. Solid-State Circuits 36, 1094–1100 (2001).

    Article  Google Scholar 

  30. Wolbarsht, M.L., Wortman, J., Schwartz, B. & Cook, D. A scleral buckle pressure gauge for continuous monitoring of intraocular pressure. Int. Ophthalmol. 3, 11–17 (1980).

    Article  CAS  Google Scholar 

  31. Mansouri, K. & Weinreb, R.N. Meeting an unmet need in glaucoma: continuous 24-h monitoring of intraocular pressure. Expert Rev. Med. Devices 9, 225–231 (2012).

    Article  CAS  Google Scholar 

  32. Mansouri, K., Medeiros, F.A., Tafreshi, A. & Weinreb, R.N. Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma. Arch. Ophthalmol. 130, 1534–1539 (2012).

    Article  Google Scholar 

  33. Flower, R.W., Maumenee, A.E. & Michelson, E.A. Long-term continuous monitoring of intraocular pressure in conscious primates. Ophthalmic Res. 14, 98–106 (1982).

    Article  CAS  Google Scholar 

  34. Xia, Y. & Whitesides, G.M. Soft Lithography. Annu. Rev. Mater. Sci. 28, 153–184 (1998).

    Article  CAS  Google Scholar 

  35. Tang, L. & Lee, N.Y. A facile route for irreversible bonding of plastic-PDMS hybrid microdevices at room temperature. Lab Chip 10, 1274–1280 (2010).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Z. Zalevsky and A. Rudnitsky for performing the Zemax simulation, S. Liu for making the molds that were used in this project and T. Halevy for making the artistic drawing of Figure 1.

Author information

Authors and Affiliations

Authors

Contributions

Y.M., S.R.Q. and I.E.A. designed the IOP sensor chip. I.E.A. and B.S. fabricated the chip. Y.M. and I.E.A. conducted the experiments and wrote the manuscript.

Corresponding authors

Correspondence to Stephen R Quake or Yossi Mandel.

Ethics declarations

Competing interests

Stanford University has applied for a patent to the US patent office on the IOP sensor technology (application number PCT/US2014/019660).

Supplementary information

Supplementary Text and Figures

Supplementary Note and Supplementary Figures 1–6 (PDF 892 kb)

Microfluidic intraocular pressure.

(a) Shift of air-fluid interface in and IOP sensor in response to pressure changes in a pressure chamber. (b) Response of IOP sensor implanted in a porcine eye to IOP modification ex vivo, as captured by a surgical microscope. (c) Response of IOP sensor implanted in a porcine eye to IOP modification ex vivo, as captured by an iPhone 4S video camera. (AVI 4954 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Araci, I., Su, B., Quake, S. et al. An implantable microfluidic device for self-monitoring of intraocular pressure. Nat Med 20, 1074–1078 (2014). https://doi.org/10.1038/nm.3621

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.3621

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing