IMPLANTABLE PARYLENE MEMS FOR GLAUCOMA THERAPY
Ellis Meng1, Po-Jui Chen2, Damien Rodger2, Yu-Chong Tai2, and Mark Humayun3
1

Department of Biomedical Engineering, University of Southern California, CA, USA
2
Caltech Micromachining Laboratory, California Institute of Technology, CA, USA
3
Keck School of Medicine, University of Southern California, CA, USA

Abstract-An implantable glaucoma management system ispresented for the first time. Glaucoma is an incurable diseasecharacterized by gradual visual field loss that eventually
results in blindness. Studies indicate that reduction ofintraocular pressure reduces the rate of disease progress. A
passive parylene MEMS pressure sensor and drainage shuntcomprise a complete system for the detection and alleviation ofelevated intraocular pressure. Tissue anchors for securing thepressure sensor to the iris have been developed to facilitate
direct and convenient optical monitoring of intraocularpressure.
Keywords – Glaucoma, glaucoma drainage devices, intraocularpressure sensor, parylene, tissue anchors

I. INTRODUCTION
Millions of people worldwide are afflicted by irreversible
vision loss attributed to glaucoma. There are often no signs
or symptoms until vision loss is severe; estimates indicatethat only half of the 3 million Americans with glaucoma areaware they have the disease [1]. The cause of the disease is
not well understood and there is currently no cure.
Glaucoma is a chronic disease and must be treated for life.
Glaucoma is characterized by pathological changes in
the optic disc and nerve fiber layer of retina. Elevated IOP> 22 mmHg is known to be responsible for slowly killing
the ganglion cell axons that comprise the optic nerve and isstrongly implicated in the pathogenesis of glaucoma [2].
Evidence from large, prospective studies suggests that
reducing IOP to normal levels (15.5±2.6 mmHg(mean±SD)) reduces the rate of disease progression [3, 4].
Glaucoma management options include medical therapy,
laser surgery, incisional surgery, and glaucoma drainage
devices (GDDs). Medical therapy lowers IOP by improving
the outflow of aqueous humor (AH) or to reduce its
production. Some surgical techniques attempt to stimulate
AH outflow, however, the primary surgical strategy is tomanage glaucoma by lowering the patients’ IOP throughremoval of excess AH. Regardless of the technique that isemployed, accurate real-time measurements of IOP and theability to restore normal levels are critical in the treatmentof this disease.
Glaucoma management typically starts frominterventions that are the safest and least invasive.
Inasmuch, medical therapy is the most widely usedtreatment initially. GDDs are used as a last resort in casesof refractory glaucoma or in patients who have notresponded to previous treatment attempts. While GDDs canpotentially lower IOP effectively, ophthalmologists arereluctant to use current GDDs due to high rates ofcomplications.

II. CURRENT GLAUCOMA DRAINAGE DEVICES
All modern GDDs are based on the 1969 concept of theMolteno implant which consists of tube that shunts aqueous
humor from anterior chamber to an external subconjunctival plate [5] . In the last 30-40 years, very few
innovative advances in surgical operation or implant devices
have occurred. Only two major modifications to GDDs
have been introduced: (1) addition of a valve to resist
outflow and reduce hypotony and (2) increase in the endplate surface area to achieve lower IOPs.
GDDs are currently limited to the treatment ofrefractory glaucoma due to complications. The mostsignificant complication of GDDs is postoperative hypotony(a condition where IOP is abnormally low, IOP <5 mmHg)[6]. During the early postoperative period, there is a lack offlow resistance prior to fibrous capsule formation around theend-plate resulting in hypotony, flat anterior chambers,choroidal effusions, and suprachoroidal hemorrhages.
Strategies to avoid hypotony include performing theoperation in two-stages to allow fibrous capsule formation,tube ligature, internal tube occlusion, and the developmentof valved GDDs. These solutions are not ideal andinterestingly, current valved implants do not perform as
advertised and do not eliminate the occurrence of thesecomplications. Furthermore, the success rate of current
GDDs decreases by 10-15% every year suggesting poor
long term performance [2].
III. MEMS GLAUCOMA THERAPY
To the best of our knowledge, no one has fabricated acomplete GDD or a passive IOP sensor using MEMS
technology. MEMS technology offers several advantagesover traditional approaches to glaucoma therapy including
highly functional microfluidic systems that can be adapted
to drug delivery and IOP management; miniaturized sensors
suitable for implantation with precise and accurate readouts[7]; precision and batch fabrication.
The purpose of a GDD is to control and regulate IOP,
however, current GDDs are lacking in function and inefficacy. These factors are partly attributed to suboptimal
design and nonideal biomaterial selection. By leveraging
polymer MEMS technology, all the components necessary
for a GDD can be seamlessly integrated into a miniaturized,
single-piece device that is biocompatible and minimizes
complications. Our MEMS GDD is an implantable, passive
parylene shunt to reduce and regulate IOP by controlling theremoval of excess aqueous humor from the anteriorchamber.

Until now, MEMS pressure sensors designed for the
purpose of IOP sensing required electrical circuitry andhermetic sealing which severely limits their implementation.
Also, tonometers fabricated using conventional techniques
are not suitable for continuous IOP monitoring and cause aconsiderable amount of patient discomfort. They typicallyrequire contact with a patient’s cornea, necessitating the useof anesthetics. We propose a new mechanical sensing
paradigm for a passive and biocompatible parylene MEMS
IOP sensor. Our sensor will be integrated with novel
parylene/silicon tissue anchors such that the sensor platform
will be implanted behind the cornea and attached to the iris
without sutures. The mechanical structure has an integrated
indicator tip that can be monitored through external optics totrack changes in IOP.
Parylene is selected as the structural material for
aforementioned components for its desirable properties,
both as a biomaterial and a MEMS material. It is a USP
Class VI material that is utilized for its biocompatibility,biostability, and low cytotoxicity. Parylene is a proven
MEMS material [8-13] with excellent properties including
low process temperature, low defect density, transparency,and chemical inertness. In addition, parylene technology
accommodates multi-layer processing to produce highly
functional structures and features.
While biologicalenvironments are extremely corrosive to most MEMS
materials, parylene is not affected as it cannot be degradedhydrolytically [14].
The combination of an implantable MEMS sensor anddrain will make it possible to closely track a patient’s IOP
history and maintain IOP at normal levels. This constitutes
a novel and complete diagnostic and therapeutic system fortreating glaucoma.

punctured using a laser to allow excess AH to be released
from the anterior chamber. Flow and pressure regulation isachieved by controlling the number of and time at which thepunctures are made along the closed end of the shunt.
Like some commercially available GDDs, this parylene
device does not prevent bi-directional flow; the laser
puncture feature does allow flexibility in initiating treatment.
Our next design will integrate a check valve to enforce oneway flow and mechanical barbs on the exterior of the tube toanchor the device and prevent slippage after implantation.
Preliminary evaluation of these shunts by implantation into
rabbit eyes also suggests the need for increased stiffness tofacilitate handling and surgical insertion of these delicate
tubes.
At physiological flow rates, pressure drops arenegligible for the size of our shunt. Therefore, the majorityof the pressure drop in the system will be concentrated at thevalve. In order to promote drainage of AH out of theanterior chamber, the valve must be optimized to drain at aflow rate equal to the production of AH at elevated IOPs. It
must open at IOP > 22 mmHg and close when IOP ≤ 22mmHg to prevent hypotony. Current GDDs with valves
have not performed as advertised and are unable to performthe shut-off function required after desired IOP levels aremet. It is suspected that once the valves open, they neverclose and possibly account for some of the observed
complications. Previously, we have demonstrated parylene
valve that can be adapted to meet all the requirements forapplication to GDDs [15]. A new biocompatible, pressuresensitive valve will based on this design will enableadvanced glaucoma management by maintaining healthy
IOP levels and achieving pressure-regulated shut-off.

IV. PARYLENE GLAUCOMA DRAINAGE DEVICEGDDs must be designed to incorporate several
physiological parameters. Aqueous humor is produced inthe eye at 2.4±0.6 µL/min (mean±SD) and changes over thecourse of a day (morning: 3.0 µL/min; afternoon: 2.4µL/min; evening: 1.5 µL/min).
The resistance of
conventional AH drainage tissues is ~3-4 mmHg/µL/min [3].
The minimal system requirements for a MEMS GDD are ashunt and pressure-sensitive valve to remove excess AH
such that IOP is maintained between 5-22 mmHg.
A parylene shunt has been fabricated using a sacrificial
silicon technology. A shunt mold is etched into a siliconwafer and parylene is deposited around the mold. Eachshunt is removed from the master mold and the silicon ischemically removed. In Fig. 1, several types of shunts areshown with one end sealed off (~8×0.5×1 mm3 and 10 µm
thick wall). At the sealed-ends, remnants of the siliconmold are visible. This closed end is implanted into theanterior chamber of the eye where it comes into contact withAH. At this end of the shunt are several regions where theparylene has been etched down to 0.5 µm or less. Whenelevated IOP is detected these thinned regions can be(a)(b)Fig. 1. (a) Parylene shunts with and without thinned regions. The dark
region at the rounded tip is silicon that has been left to provide contrast forviewing. (b) Mechanism of AH release through laser-induced punctures inthinned regions.

V. SPIRAL-TUBE PARYLENE IOP SENSOR
Our mechanical pressure sensor is based on theprinciple of operation of a Bourdon tube [16] and consists ofa centrally supported, free-standing parylene spiral-tube
formed by a long, thin-walled toroidal channel (Fig. 2). An
indicator tip is integrated at the end of the channel at thecircumference of the spiral as a means for simple opticalreadout. A detailed report on the fabrication of the device isdescribed in [17].
The hollow spiral channel forming the sensor is sealed
at 1 atm as the gauge reference. When a uniform pressure
difference is generated across the channel walls, a bending
moment is created forcing an in-plane radial and angulardeformation of the tube. When the external pressure islower than the internal pressure in the channel, the spiralstructure unwinds. When the external pressure exceeds theinternal pressure, the spiral will further coil. This effect canbe monitored by visually tracking the movement of theindicator tip. Deformation that results is linearly related tothe applied pressure difference and can be correlated toenvironmental pressure, or in this case, IOP.

Fig. 2. SEM of passive, spiral-tube parylene IOP sensor (1 mm radius) andclose-up of integrated indicator tip (6×100 µm)

Measured Pressure Difference (psi)

87
65
4
3
testing01
testing02
testing03

2
100

5

1015

20

25

30

3540

Observed Tip Rotation (degree)

Fig. 3. Observed tip rotation in water under applied pressure.

45Sensor operation has been verified in air, isopropyl
alcohol (IPA), and water. Observed tip rotation is visually
recorded with the aid of optical magnification as theenvironmental pressure is increased. The results for water
are shown below (Fig. 3). Measured sensitivities are
0.22 °/mmHg (± 9% variation in rotation angles) in IPA and0.13 °/mmHg in water (± 15% variation). Sensitivity of thepressure sensor can be tuned by changing the number of coilturns. Increased sensitivity can be achieved by increasing
the number of coil turns, decreasing the thickness of thetube walls, and increasing the aspect-ratio profile of the tube.
Preliminary implantation studies in rabbits indicate thatthe spiral-tube structure lacks the necessary mechanicalrobustness to survive surgery. Currently, efforts to further
reduce the overall device size and integration of a protective
cap are underway to facilitate implantation. In addition toimproving device reliability, design optimization is being
investigated to increase sensitivity.
VI. SUTURE-LESS TISSUE ANCHORS
Implantable devices require mechanical attachment tothe biological environment. This is typically achieved bysutures, tacking, or stapling at the expense of increasing
overall implant size through the addition of anchoring sites.
Given the spatial constraints in the eye and to minimize
damage, it is desirable to implant and secure our sensor andGDD without needing sutures.
The logical choice for placement of the IOP sensor tofacilitate optical readout would be behind the transparent
cornea on the iris. In order to monitor movement of theindicator tip, the sensor should be securely attached to theiris. The surface topology of the iris consists of numerous
folds resembling hills and valleys that can accommodate
alternative mechanical attachment methods. We fabricatedand implanted two tissue anchoring prototypes consisting of
Velcro-like arrays of parylene-covered silicon posts on theirises of rabbit eyes (Fig. 4).
Fabrication of the posts can be integrated with the IOP
sensor process. To enhance the adhesion of parylene,anchors are patterned and etched at future post sites
following [18]. Posts are then defined and etched using
DRIE in a silicon substrate. Finally, the entire structure iscoated with a biocompatible parylene layer.
The etched columnar anchors securely fastened siliconplates to rabbit irises. The plates remained fastened evenafter vigorous shaking imposed on the eye by the surgeon.
The force required to dislodge anchored structures will bedetermined. Currently, these structures are being integrated
on the backside of an IOP sensor substrate and will be used
to hold the entire platform in place for visual inspection ofIOP. Similar anchoring structures may also be applied tomechanically attach the GDDs.

Top

Bottom(a)(b)Fig. 4. (a) 3D illustration of IOP sensor on a silicon platform (1.5 mm× .75 mm) with integrated tissue anchors underneath. (b) Fabricatedanchors showing different layouts and views (top and side). The circularanchor in the top left is 250 µm in diameter and 250 µm long. The squareanchors measure 250 µm on a side and the radial arms in the lower left
photo are 8 µm in width.

VII. CONCLUSION
Implantable parylene MEMS for complete managementof glaucoma, including monitoring and therapy, arepresented.
Preliminary results of implanted systemcomponents into rabbits are extremely promising. Current
work in progress includes careful examination of
biocompatibility and implantation challenges andoptimization of system components for application inhumans.
ACKNOWLEDGEMENT
This work was supported in part by the Engineering
Research Centers Program of the NSF under Award
Number EEC-0310723 and by a fellowship from theWhitaker Foundation. We would like to thank Mr. Trevor
Roper for assistance in fabrication, Dr. Murat Tunc for
performing surgical implantations, and Dr. Tuan Hoang forhelp with proofreading.
REFERENCES[1] "Glaucoma Facts," Glaucoma Research Foundation,
http://www.glaucoma.org/learn/facts.html.
[2] C. H. Hong, A. Arosemena, D. Zurakowski, and R. S.
Ayyala, "Glaucoma drainage devices: a systematic literature

review and current controversies," Surv Ophthalmol, vol. 50,
pp. 48-60, 2005.
[3] C. R. Ethier, M. Johnson, and J. Ruberti, "Ocularbiomechanics and biotransport," Annu Rev Biomed Eng, vol.
6, pp. 249-73, 2004.
[4] K. Schwartz and D. Budenz, "Current management ofglaucoma," Curr Opin Ophthalmol, vol. 15, pp. 119-26,
2004.
[5] A. C. Molteno, "New implant for drainage in glaucoma.
Clinical trial," Br J Ophthalmol, vol. 53, pp. 606-15, 1969.
[6] Q. H. Nguyen, "Avoiding and managing complicationsof glaucoma drainage implants," Curr Opin Ophthalmol, vol.
15, pp. 147-50, 2004.
[7] W. Mokwa and U. Schnakenberg, "Micro-transponder
systems for medical applications," IEEE Transactions on
Instrumentation & Measurement, vol. 50, pp. 1551-5, 2001.
[8] X. Q. Wang and Y. C. Tai, "A Normally Closed InChannel Micro Check Valve," in MEMS 2000. Miyazaki,Japan, 2000.
[9] J. Xie, Q. He, Y.-C. Tai, J. Liu, and T. Lee, "Integrated
Electrospray Chip for Mass Spectrometry," in mTAS 2002.
Nara, Japan, 2002, pp. 709-711.
[10] J. Xie, J. Shih, and Y.-C. Tai, "Integrated SurfaceMicromachined Mass Flow Controller," in MEMS '03.
Kyoto, Japan, 2003.
[11] Q. He, E. Meng, Y.-C. Tai, C. M. Rutherglen, J.
Erickson, and J. Pine, "Parylene Neuro-Cages for Live
Neural Networks Study," in Transducers 2003. Boston, MA,2003, pp. 995-998.
[12] E. Meng, S. Aoyagi, and Y.-C. Tai, "High Aspect Ratio
Parylene Etching for Microfluidics and BioMEMS," inMicro Total Analysis Systems 2004, vol. 2. Malmo, Sweden,2004, pp. 401-3.
[13] E. Meng and Y.-C. Tai, "Polymer MEMS for Micro
Fluid Delivery Systems," in Polymer Preprints, vol. 44.
New York, New York, 2003, pp. 552-553.
[14] J. I. Kroschwitz, "Kirk-Othmer Encyclopedia of
Chemical Technology," Fourth ed. New York: John Wiley& Sons, Inc., 1998.
[15] E. Meng, X.-Q. Wang, H. Mak, and Y.-C. Tai, "ACheck-Valved Silicone Diaphragm Pump," in MEMS 2000.
Miyazaki, Japan, 2000.
[16] R. A. Clark and E. Reissner, "Deformations andstresses in bourdon tubes," Journal of Applied Phyics, vol.
21, pp. 1340-1, 1950.
[17] P.-J. Chen, D. Rodger, M. Humayun, and Y.-C. Tai,
"Spiral-Tube Parylene Intraocular Pressure Sensor," inMEMS 2005. Miami, FL, 2005, pp. 311-4.
[18] M. Liger, D. C. Rodger, and Y. C. Tai, "Robust
Parylene-to-Silicon Mechanical Anchoring," in MEMS 2003.
Kyoto, Japan, 2003, pp. 602-605.