MEMS based Intraocular Pressure Monitor

Anil Kumar RamRakhyani, Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, USA

AbstractGlucoma is a neurogenerative eye disease and generally characterized by elevated intraocular pressure (IOP). Traditionaly tonometer based IOP monitor systems were used that are uncomfortable for patient and provides low measurement resolution. To reduce the chances of glucoma, perdioic monitoring of IOP in the eye is important and requires an implantable IOP monitor system. With the advancement of MEMS technology and its integration with the CMOS process, a small MEMS based implantable pressure sensor can be fabricated. In this work, three MEMS based approaches are compared and one design approach is studied based on LC resonator for IOP monitoring [1]. The key limitation of this design was high pressure resolution of 1 mmHg. To increase the measured pressure resolution to sub-mmHg values, a Resonance based Readout Circuit with Frequency Locking is proposed that can achieve resolution below 0.1 mmHg.

accurate. With the advancements in IC technology and its integration with the MEMS sensors, small implantable IOP sensors are possible. Key requirements of the future IOP measurement devices includes sub-mmHg accuracy, small dimensions, and minimal invasiveness. In recent years, three design approaches were taken utilizing MEMS based sensor and ASIC designs. The rst approach utilizes strain gauge sensor embedded in the contact lens. The second approach utilizes passive LC resonator based implant. The third method is based on MEMS based pressure sensor with supporting electronics and data communication ASIC. In the following section, recent advancements in each method is studied with the key benets and limitation of each technology. II. I MPLANTABLE IOP M ONITOR Strain gauge based lens is highly accurate method to measure IOP with the accuracy of 0.2mmHg [4]. With the change in IOP, the curvature of the lens changes causing a strain in the lens embedded wire. This technique is non-invasive and doesnt require surgery. Its detection mechanism doesnt depend on the electrical properties of the tissue making these lens very robust. Despite the above advantages of the IOP lens, this mechanism requires a precise fabrication of the lens based on the eye curvature. Thus depending on the patient, the lens design needs to be personalized. The measurement electronics includes wireless powered active circuit and telemetry system. Due to high personalization cost of the lens, this approach has a high commercialization cost and requires further investigation for self calibration. The LC resonator based IOP sensor is an interesting method which utilizes the MEMS based capacitance pressure sensor to measure IOP. The design requires implantation of passive LC resonator for which the resonating frequency varies with the change in pressure controlled MEMS capacitance. To measure the resonating frequency of the implant coil, a inductively coupled external coil is used. It measures the effect of the implant coil on the external coil impedance. With the accurate measurement of phase shift in the impedance, the resonance frequency of the implant coil can be calculated. Due to simple design and the possibility of small dimensions, this method has got considerate attention as an alternative technology for the IOP measurement. Key benets includes zero power implant and patient independent design. The sensitivity of the measurement highly depends on the coupling between the measuring and the implant coil and the Q-factor of the implant coil. For the practical design IOP resolution of 2.5mmHg was

I. I NTRODUCTION Glucoma is a neurodegenerative condition that causes blindness in more than 60 million people worldwide [2]. Intraocular pressure (IOP) is the balance between the body generated aqueous humor and its outow. For a healthy eye, aqueous humor drains through the schelms canal and the episcleral veins [3]. With the unbalanced outow of humor, intraocular pressure elevates resulting in higher chances of glucoma. There are other reasons also that can result in elevated IOP as compared to a healthy eye. However, IOP is a direct measurement for the early detection of glaucoma. IOP varies between 10-21 mmHg for healthy eyes and small increase in IOP ( 1 mmHg) can indicate high chances of glaucoma in patients. During the different state of a body (sleep or awake), IOP can uctuate signicantly. Thus a single measurement of IOP may not be the best measure for the early detection of glucoma. An accurate measure of IOP requires multiple measurements over 24 hours. Traditionally, tonometer based IOP measurement devices were used which are painful, low resolution, error prone, and require expert technicians for the measurements. These methods include Goldman tonometer and the Tono-pen. These devices utilizes the applanation principle utilizing the relationship between the force, pressure and area. Currently Goldmann tonometer is standard procedure. However, this procedure is highly uncomfortable for the patient and requires local anaesthesia to keep the eye open during the procedure. The tonometers head touches the cornea and thus requires an expert technician to align the instrument with the patient. Due to the requirement of a sophisticated setup, multiple measurements of IOP over a single day is not possible. Thus state of the art procedures for IOP measurement are not

achieved [1]. Few designs were able to achieve high resolution of 0.5 mmHg [5]. However, in-vivo testing is still under way. Self resonating frequency of the implant coil is highly susceptible to the permittivity of the surrounding medium. Thus, the Q-factor of the implant coil drops considerably after implantation and requires the measuring coil to be in close proximity with the implant ( 1.5-2.0 cm). MEMS based capacitance pressure sensor measures the change in the MEMS capacitance due to change in IOP. The implanted electronics can monitor the IOP periodically and store the capacitance change data in the on site nonvolatile memory [6][8]. The data can be transferred to the external readout system using an implanted antenna. Pressure resolution of 1.3mmHg [7] was measured on a mouse model. Due to the implanted IOP sensor and communication ASIC, a high frequency wireless power transfer need to be deployed based on rectenna. Thus requires a external power supply. Implantable IOP sensors provide a benet of periodic monitoring, reduced cost, and higher comfort as compared to a standard tonometer. Three deign approaches provide different technology advancements. However, LC resonator based IOP monitor is found to be simpler, patient independent and low power as compared to the other approaches. Recently, the LC resonator based IOP monitor was implanted and in-vivo experiments were performed on a rabbit eye model [1], [9]. In this work, LC resonator based design is implemented due to its ability of utilizing passive implants to measure IOP and critical review is performed for published work with exible coil based MEMS IOP monitor system [1]. III. S TUDY OF F LEXIBLE COIL LC R ESONATOR BASED IOP MONITOR [1] MEMS capacitor based pressure monitoring are a commonly used technique used for commercial and medical applications. LC resonator based IOP monitor was rst proposed with a MEMS capacitor and a wire wound coil [10]. Since then many designs were implemented using the same underlying principle of phased-dip monitoring due to resonating coil [1], [5], [9]. Few designs utilized electroplated inductor to reduce the dimensions of implant below 2.6 1.6mm2 [5]. In the selected paper, to increase the biocompatibility of the coil and to achieve a mechanically soft coil, a exible coil is fabricated using multilayer parylene micromachining and deep silicon etching technology [1]. The following section describes the underlying theory and fabrication process of the IOP monitoring system. A. Theory of Operation Figure 1 shows the block diagram of the passive electrical sensing of IOP using phased-dip principle. For continuous monitoring of IOP, an external coil is fed with a time varying sinusoidal signal which causes current in the implant coil. If the operating frequency is the same as the resonance frequency of the implant coil, the reected load of the implant at the external coil is maximum. In terms of impedance, the

equivalent impedance Zeq can be calculated based on Equation 1 [1].

Fig. 1. Block diagram of Traditional LC resonator based IOP monitor system [1].

Zeq ( f ) = j2 f L p 1 + k2 1
f fs

f fs 2

1 Qs f fs

(1)

where L p is the inductance of the external readout coil, fs is the resonance frequency of the implanted LC resonator, k Ls is the magnetic coupling between the coils and Qs = 2 Rs . When the external coil is driven at fs , the impedance Zeq can be written as Equation 2. Zeq ( f ) = j2 f L p (1 + jk2 Qs ) (2)

and the phase of the impedance has a magnitude dip approximated by = tan1 (k2 Qs ). It can be seen that the phase dip is strongly dependent of the coupling between the coils and thus limits the operating range of the readout coil. To increase the sensitivity of measurement, the Qs need to be maximized and in general a Q-factor of 30 45@ fs = 350 MHz was achieved using parylene supported metal layers. The pressure sensitive variable capacitor is connected to the coil which is embedded in a deformable diaphragm chamber. With the change in the IOP value, the diaphragm deformation varies causing change in the variable capacitance. The external coil is driven with a range of frequencies to scan the resonating frequency of the implant coil. Thus, the implants resonance frequency can be calculated by measuring the frequency where maximum phase dip is achieved. B. Fabrication Process The key design objective of the paper was to achieve a small exible coil to reduce the size of the suture. For an incision less than 2 mm, the eye can heal spontaneously and thus doesnt require a suture after implantation [1]. The fabricated coil is of the diameter 4 mm and can be folded to 1.5 mm during implantation (Figure 2). Due to high yield strain of parylene C, the exible coil stretches back to its original circular shape without any change in inductor characteristics. To fabricate the microsensor, a sacricial PR layer is used. The metal layer is ebeam evaporated and sandwiched between the top and bottom parylene C coats. The sensor packaging is done in air under

atmospheric pressure. To create air chamber for the pressure sensing, a non-electric piece was attached using biocompatible epoxy. To create the tissue anchor, a exible ophthalmic iris retractor was attached to the non-electronic side of the sensor using biocompatible epoxy. Figure 2 shows the conguration of the fabricated coil based on [1].

Fig. 2.

Flexible implantable IOP sensor [1].

C. Results Using 4-turn exible coil an inductance of 57 nH was achieved with the Q-factor of 30 at the resonant frequency of 350 MHz. To characterize the sensor, an on-bench pressure sensing was done in a pressure chamber. Using a controlled pressure setup, an accurate pressure range can be created with P = Poutsidesensor Pinsidesesnor . Due to change in pressure, the shift in minimum phase frequency can be noted based on Equation 3, 4. fmin ( P) fmin ( P = 0) Cs Cs

f or

Cs

Cs

(3) (4)

= (1

P)1/2

where is the parameter incorporating the mechanical behaviour of diaphragm. In the current work, a sensitivity of 455 ppm/mmHg was achieved which reects the responsivity of 160 kHz /mmHg. To reduce the noise oor of the measurement, multiple scans were taken and a SNR 10 was achieved with the average phase noise of 0.0015o with 80 samples averaging. For the external coil to iris distance of 1.5-2 cm, an accuracy of 1 mmHg was achieved. However in close proximity of lossy conductive tissue, the Qfactor of the coil drops to 3-4 which was further improved to 20 by using 10 m thick parylene coating on the coil. The practical pressure resolution of 2.5 mmHg was reported. D. Discussion The feasibility of a exible implant coil for IOP monitoring increases the possibility of sutureless surgery. However, the current design achieves low pressure sensitivity that need to

be addressed for practical IOP measurements. The following section discusses about the key limitations of the design and possible approaches by which the authors can make a better design. 1) Operating Frequency: The operating frequency of the resonator is a key design parameter. In general, it is restricted by the zero pressure MEMS capacitance and implemented inductor. In current design 4-turn inductor provides very small inductance of 57 nH resulting in the resonance frequency of 350 MHz. As this implant will be embedded in lossy conductive tissue thus a trade-off between the operating frequency and Q-factor off the coil in tissue needs to be taken into consideration. In previous IOP based design, the resonance frequency near 70 MHz was taken [5], [9]. 2) Readout Circuit: LC resonator based IOP monitor uses impedance meter to measure the magnitude and phase of the equivalent impedance of external coil in close proximity of the implant. In current design, the average phase error of 0.001o was achieved using network analyzer. In general, network analyzers are high performance devices and are customized to achieve low phase noise. For a practical design, a low power standalone readout circuit needs to be designed achieving same phase noise of 0.001o or lower. The nal readout circuit needs to be small enough to be mounted on the human patients. 3) Environmental Conditions: LC resonator based IOP monitor characterize the electrical properties of the implant coil. The surrounding medium of the implant (such as tissue) has signicant effect on the system performance. Due to high conductive losses in the tissue, the Q-factor of the implant drops signicantly which results into a higher measurement error for the intra-ocular pressure. Thus the effect of the surrounding tissue needs to be considered during the design stage. 4) Resolution: For early detection of glucoma, a sub-mmg resolution in IOP monitoring is required. Due to low coupling between the implant coil and readout coil, the LC resonator based monitor mechanism suffers from a high measurement error.In this work [1], a pressure resolution of 1 mmHg was reported on the test bench. However, for practical scenario a resolution of 2.5 mmHg was reported after implantation in rabbits eye. Despite of a low design cost and zero power implant, LC resonator based IOP monitor system needs to overcome this challenge to achieve sub-mmHg pressure resolution. 5) Effect of Flexible coil: In this design, a single layer 4-turn spiral coil is fabricated for the implant which limits the inductance of the coil to very low value. Traditionally, multi-layer coils were used to keep the the zero-pressure resonance frequency to 30-70 MHz [5], [9]. However, exible coil restricts the use of multi-layer coil due to high mechanical stress. Thus, for a given implant size, exible coil looses one design parameter of multi-layer coil design to bring the operating frequency to a low value. IV. P ROPOSED T ECHNIQUES To keep the same benets of the MEMS LC resonator as an implant and to reduce the measurement error of the system,

the following steps are recommended. A. Full System Optimization To utilize the trade-off between the Q-factor of the implant coil and conductive losses in tissue, the operating frequency needs to be chosen carefully. The value of the MEMS capacitor at zero pressure depends on the available size on the IOP implant. Thus, to tune the operating frequency, the exible coil need to be optimized for number of turns, width of the traces, and distance between the coil traces. FDTD (nite difference time domain) simulations of the external and implant coils need to be done as part of the design cycle to accurately calculate the effect of tissue on the Q-factor of the coil. B. Resonance based Readout Circuit with Frequency Locking To increase the resolution of the LC resonator based IOP monitor system and to relax the requirement of low phase noise impedance analyzer, a resonance based readout circuit is proposed in the following section. Figure 3 shows the block diagram of the proposed system to increase the pressure resolution of current design. Resonance based read-out circuit works on the principle that when two resonators are operated on the same resonance frequency, the effect of one is maximum on the other. As shown in the Figure 3, the read-out circuit consists of a quadrature output voltage controlled oscillator connected to a external coil and a voltage tunable capacitance. Using a control signal for the frequency-sweep in VCO, the input signal of the external coil is varied to cover the frequency range of implant coil resonance corresponding to P = 0 to P = 50 mmHg. Using a tunable capacitor (MEMS based), the external coil is always kept at the resonance during the frequency sweep cycle. Due to the close proximity of the implant coil (1.5-2.5 cm), the equivalent impedance at the primary side can be calculated based on Equation 5.

where L p and C p are the inductance and capacitance of the read-out circuit, respectively. R1 = Rsense + R parasitic of the external circuit. w p and wr are the VCO frequency and the resonance frequency of the implant LC resonator at any pressure. Due to resonance condition at the read-out circuit, Equation 5 can be simplied as Equation 6 Zeq = R1 1 + k2 Q p Qs
wr 1 + jQs 1 w 2
2 p

(6)

where Q p = For ws = has zero reactance and VCO output frequency at the resonance frequency of the implant, the voltage across the sense resistor is modulated with the quadrature signal of the VCO and lter using a low pass lter (LPF) to remove the second order harmonics. The voltage across the sense resistor and modulator output can be written in phasor form as shown in Equation 7 and Equation 8. = Rsense Isense = Rsense |Vvco |e jw p t Zeq
o)

wpLp w p Ls R1 and Qs = R2 . w p , the equivalent impedance Zeq Zeq = R1 (1 + k2 Q p Qs ). To lock the

VRsense VmodulatorOut

(7) (8)

= VRsense |Vvco |e j(w p t +90

When VCO output signal locks to the implant resonance frequency (w p = ws ), imaginary(Zeq ) = 0 and modulator output doesnt have any DC-component (zero-Hz component). However, when w = w p ws = 0, the DC-component VDC of the modulator output can be calculated based on Equation 10. Zeq w = |Zeq |e j R1 1 + k2 Q p Qs 2 jk2 Q p Q2 s wp w 2 k 2 Q p Q2 s wp 1 = tan (9) 1 + k2 Q p Qs = 1 Rsense |Vvco |2 sin( ) 2 |Zeq | (10)

VDC

Fig. 3. Block diagram of proposed Resonance based Readout Circuit with Frequency Locking to measure IOP.

Zeq = (R1 + jw p L p +

w p L p Qs 1 ) + k2 2 jw pC p 1 + jQ 1 wr
s

(5)

w2 p

Moreover, the read-out circuit doesnt require expensive VNA for phase characterization and can be easily embedded in the patients glass. When VCO output frequency locks with implant resonance frequency, the frequency can be calculated using VCO control voltage versus frequency relationship. With the knowledge of resonance frequency, pressure can be calculated based on Equation 4. 1) Feasibility Study: To check the feasibility of the proposed Resonance based Readout Circuit with Frequency Locking technique, the same dimension of the implant coil, external coil, and operating distance are taken based on work [1]. A high gain sensing amplier can be used with negative feedback to get a gain factor of 100. To generate the feedback signal resolution of 1 mV, the sensing circuit input voltage resolution of 10 V will be sufcient. To eliminate the 1/ f

noise from amplier, the VDC can be modulated to intermediate frequency fm , amplied and then demodulated back to DC. To measure VDC , the minimum required w can be calculated based on Equation 9 and Equation 10. In the presented design [1], k = 0.002 for 25 mm operating distance between the single turn 3 cm radius external coil (L p = 180 nH and 2 mm radius implant coil (Ls = 57 nH ). Rsense = 1, Q p = 200@350MHz, R1 = 2 and Qs = 30 results to k2 Q p Qs = 0.024. To control the resonance condition in the external coil, metal based MEMS based capacitor Cp (C p = 1.136 pF) with 5% tuning range (Q-factor 600-700 @350 MHz) will be sufcient to sweep the frequency from 344 MHz (for P = 50 mmHg) to 352 MHz (for P = 0 mmHg) [11], [12]. Near locking condition, w w p thus Zeq R1 (1 + k2 Q p Qs ) = 2.048. For VDC(min) = 10 V and |Vvco | = 1 V, sin( ) = 40.96e-6 radians (or 0.0023 in degrees). For small 0, sin( ) = resulting minimum detectable phase difference due to frequency mismatch is min = 40.96e-6 radians. For small 0, tan( ) = , thus the minimum detectable w can be calculated based on Equation 11. w p ws = w = wp (1 + k 2 Q p Q s ) 2k2 Q p Q2 s

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[1] P.-J. Chen, S. Saati, R. Varma, M. Humayun, and Y.-C. Tai, Wireless intraocular pressure sensing using microfabricated minimally invasive exible-coiled lc sensor implant, Microelectromechanical Systems, Journal of, vol. 19, no. 4, pp. 721 734, aug. 2010. [2] P. D., V.-C. P., and V. E., Imodern monitoring intraocular pressure sensing devices based on application specic integrated circuits, Journal of Biomaterials and Nanobiotechnology, vol. 3, no. 2, pp. 301309, jan. 2012. [3] K. Katuri, S. Asrani, and M. Ramasubramanian, Intraocular pressure monitoring sensors, Sensors Journal, IEEE, vol. 8, no. 1, pp. 12 19, jan. 2008. [4] M. Leonardi, E. M. Pitchon, A. Bertsch, P. Renaud, and A. Mermoud, Wireless contact lens sensor for intraocular pressure monitoring: assessment on enucleated pig eyes, Acta Ophthalmologica, vol. 87, no. 4, pp. 433437, 2009. [5] O. Akar, T. Akin, and K. Naja, A wireless batch sealed absolute capacitive pressure sensor, Sensors and Actuators A: Physical, vol. 95, no. 1, pp. 29 38, 2001. [6] E. Chow, S. Chakraborty, W. Chappell, and P. Irazoqui, Mixed-signal integrated circuits for self-contained sub-cubic millimeter biomedical implants, in Solid-State Circuits Conference Digest of Technical Papers (ISSCC), 2010 IEEE International, feb. 2010, pp. 236 237. [7] D. Ha, W. Vries, S. John, P. Irazoqui, and W. Chappell, Polymer-based miniature exible capacitive pressure sensor for intraocular pressure (iop) monitoring inside a mouse eye, Biomedical Microdevices, vol. 14, pp. 207215, 2012. [8] E. Chow, A. Chlebowski, and P. Irazoqui, A miniature-implantable rf-wireless active glaucoma intraocular pressure monitor, Biomedical Circuits and Systems, IEEE Transactions on, vol. 4, no. 6, pp. 340 349, dec. 2010. [9] P.-J. Chen, D. Rodger, S. Saati, M. Humayun, and Y.-C. Tai, Microfabricated implantable parylene-based wireless passive intraocular pressure sensors, Microelectromechanical Systems, Journal of, vol. 17, no. 6, pp. 1342 1351, dec. 2008. [10] L. Rosengren, Y. Backlund, T. Sjostrom, B. Hok, and B. Svedbergh, A system for wireless intra-ocular pressure measurements using a silicon micromachined sensor, Journal of Micromechanics and Microengineering, vol. 2, no. 3, p. 202, 1992. [Online]. Available: http://stacks.iop.org/0960-1317/2/i=3/a=021 [11] D. J. Young and B. E. Bose, A micromachined variable capacitor for monolithic low-noise vcos, in IEEE Solid-State Sensor and Actuator Workshop, June 1996, pp. 8689. [12] J.-B. Yoon and C.-C. Nguyen, A high-q tunable micromechanical capacitor with movable dielectric for rf applications, in Electron Devices Meeting, 2000. IEDM 00. Technical Digest. International, 2000, pp. 489 492.

(11)

For = 40.96e-6 radians, w is around 10 kHz. Thus the proposed technique can accurately lock the VCO frequency to the implant coil resonance frequency. It corresponds to the pressure resolution of 0.064 mmHg for responsivity of 160 khz/mmHg of the implant coil. Even if the minimum required input voltage of 0.1 mV (instead of 10 V ) at the amplier input, the pressure resolution of 0.64 mmHg can be achieved. The proposed IOP monitor system is expected to consume less than 0.5 mW power for periodic IOP monitoring in each 5 minutes. In practical scenario, the minimum detectable phase will be determined by the VCO phase noise which will still be less than the 1 mmHg pressure resolution. As minimum detectable phase min V1 2 , thus proposed vco systems sensitivity can be further improved using higher Vvco . V. C ONCLUSION In this work, a LC resonator based IOP monitor is studied and its key design parameters are identied based on [1]. Even if the LC resonator provides simple and low cost architecture, however the monitor mechanism suffers from high measurement error. During the design stage, the effect of tissue need to be modeled to optimize the coil and to calculate the operating frequency of the system. Moreover, using the proposed Resonance based Readout Circuit with Frequency Locking 16 times higher accuracy can be achieved using the same implant design and operating conditions. The proposed system doesnt require a costly and bulky VNA for resonance frequency measurement and utilizes a robust negative feedback to lock the read-out circuit VCOs output frequency to the implant coil resonance frequency. To the best of author knowledge, the proposed technique is not been used before for IOP monitoring.