**4.2 Fold-and-bond coil**

12 Microelectromechanical Systems and Devices

Cs = 201 pF. The theoretical numbers are also calculated using the abovementioned equations, and the fitting curves are plotted in Fig. 8, in comparison with the measured curves. The experimental data matches the theoretical calculations closely, with deviations of less than 19%. These errors may be attributed to the simplification of the 3-element model as well as interferences from the measurement instruments. The Q factor of the coil is obtained to be approximately 0.1 at the target frequency of 1 MHz, as expected from the

Fig. 8. Impedance measurement and curve fitting using the 3-element model: (a) Imaginary part; (b) Real part. (Red curves correspond to theoretical parameters of the fabricated coil:

The data and power transfer performances have also been verified using a custom designed data link at the University of California, Santa Cruz (UCSC). The testing waveforms are shown in Fig. 9, where the blue curve represents the data driving signal on the primary stage, the green curve represents the voltage across the primary coil, and the purple curve

Fig. 9. Inductive coupling test waveforms: (a) received signal is 25 mV peak to peak;

While successful data transmission through our coils has been demonstrated, it is noted that this device has no driving capability due to its small Q factor (~ 0.1), meaning that the power cannot be delivered to the load. Therefore, enhancing coil's Q factor to achieve a higher power transfer efficiency is crucial for designing the next generation of coils.

design.

Ls = 1.0 µH, Rs = 67 Ω and Cs = 183 pF.)

(b) received signal is 15 mV peak to peak.

represents the receiving voltage across the secondary coil.

In the concept of fold-and-bond technology (Fig. 10), two or more thin-film planar spiral coil segments are fabricated from the same batch so that each segment has identical selfinductance and ESR, denoted by Ls and Rs, respectively. A new coil can then be formed by stacking *n* segments together in either parallel or series connections. For parallel stacking, particularly, the new coil will have identical inductance but *n*-times larger in equivalent metal thickness, resulting in an *n*-times lower ESR. As for series stacking, the resistance remains the same while the inductance increases by *n*-times because of the mutual inductance between adjacent layers. According to the definition of the Q factor, both approaches can achieve an *n*-times Q factor enhancement. In this section, the series stacking configuration is used to demonstrate the technology concept.

Fig. 10. Concept of the fold-and-bond technology for Q factor enhancement. A coil with one fold is depicted for representation.

Fold-and-bond coil's fabrication involves the dual-metal-layer Parylene/metal skin realization and a post-fabrication thermal bonding process (Li et al., 2008). The Parylenemetal skin with two buried layers of metal is first fabricated in the same manner as described in Fig. 5, in which one layer of metal is used to form the conductive wires of the coil, while the other layers is used to make the interconnections between the layers. This thin film skin can be folded and stacked into multiple layers because of the flexibility of Parylene C. While hand alignment under an optical microscope is used at the current stage, special alignment jigs can be custom designed in the future to achieve precise

Implantable Parylene MEMS RF Coil for Epiretinal Prostheses 15

(a) (b)

Fig. 12. Devices after thermal bonding: (a) Fold-and-bond coils after thermal bonding. (b)

(a) (b) Fig. 13. (a) Demonstration of device's flexibility; (b) Stretching marks along the folding line. The electrical characteristics of the fabricated fold-and-bond coils are studied before and after thermal bonding. The lump parameters are extracted from the same 3-element model, as summarized in Table 3. As expected, the self-inductance and Q-factor of the coil are increased by more than 90% for both coil designs after folding. Changing the wire width has no significant impact on the parasitic capacitance, indicating the capacitance between adjacent layers is dominant over the capacitance between turns. Coil prototype I shows a much higher ESR compared to its theoretical value (29 Ω), which may be attributed to the non-uniformity of metal thickness. Overall, the measured values show good agreement with the theory predictions, demonstrating that the theoretical model can predict the coil

Type Rs (Ω) Ls (µH) Cs (pF) Calculated Q at 1MHz Q Increase

<sup>I</sup>Before 41.2 2.9 -- 0.44 -- After 41.8 5.7 62.1 0.85 95% II Before 91.3 8.6 -- 0.58 -- After 92.2 16.3 70.8 1.11 91% Table 3. Measured electrical parameters of fold-and-bond coils using the 3-element model.

Overlapping metal wires with misalignments of 10 µm to 30 µm.

properties effectively.

alignment of different layers. During the thermal bonding procedure, the folded device is sandwiched between two glass slides covered with aluminum sheets, which can avoid Parylene sticking on the glass. The whole unit is placed in a vacuum oven and bonded at 230 ºC for two days. External pressure can be applied as needed to enable Parylene-Parylene bonding at moderate temperatures. The vacuum pressure is controlled at ~ 10 Torr to prevent Parylene C from unwanted oxidation in air at an elevated temperature.

Two Parylene-based skins with dual-layer embedded metal have been fabricated, as shown in Fig. 11. These prototypes are specifically designed for intraocular retinal prosthesis with the design parameters described in Table 2. The thickness of metal wires is increased to ~ 2 µm in order to further reduce the coil's DC resistance. The metal is covered with ~ 3.4 µm Parylene C on each side with the lead contact vias open. Fig. 12 shows the final devices after folding and thermal bonding. Misalignments of 10 µm to 30 µm have been observed, which is due to the lack of control with the hand alignment.



Fig. 11. Devices before thermal bonding: (a) Fabricated dual-metal-layer Parylene-based skins; (b) Microscope image of an interconnection via between two metal layers; (c) Photos of device details (from left to right): conductive wires of the coil, folding junction and suturing holes.

The devices still remain flexible after bonding (Fig. 13 (a)), indicating that annealing at a temperature below the melting point of Parylene C (290 ºC) (Harder et al. 2002) will not alter the mechanical flexibility of the material. The DC resistances of the samples are measured before and after bonding with no significant change observed (Table 3), confirming the ductility and durability of metal traces. Stretching marks and Parylene cracks are found along the folding line after thermal treatment, which is caused by stress concentration during folding. Additional Parylene coating can be performed after thermal bonding to conformally cover these cracks in order to ensure a good sealing for final devices.

alignment of different layers. During the thermal bonding procedure, the folded device is sandwiched between two glass slides covered with aluminum sheets, which can avoid Parylene sticking on the glass. The whole unit is placed in a vacuum oven and bonded at 230 ºC for two days. External pressure can be applied as needed to enable Parylene-Parylene bonding at moderate temperatures. The vacuum pressure is controlled at ~ 10 Torr to prevent Parylene C from unwanted oxidation in air at an elevated temperature. Two Parylene-based skins with dual-layer embedded metal have been fabricated, as shown in Fig. 11. These prototypes are specifically designed for intraocular retinal prosthesis with the design parameters described in Table 2. The thickness of metal wires is increased to ~ 2 µm in order to further reduce the coil's DC resistance. The metal is covered with ~ 3.4 µm Parylene C on each side with the lead contact vias open. Fig. 12 shows the final devices after folding and thermal bonding. Misalignments of 10 µm to 30 µm have been observed, which

Type Total number of turns Rs (Ω) Ls (µH) Cs (pF) Q at 1MHz I 28 29 2.9 65.5 1.1 II 48 90 14.8 64.5 1

Fig. 11. Devices before thermal bonding: (a) Fabricated dual-metal-layer Parylene-based skins; (b) Microscope image of an interconnection via between two metal layers; (c) Photos of device details (from left to right): conductive wires of the coil, folding junction and

The devices still remain flexible after bonding (Fig. 13 (a)), indicating that annealing at a temperature below the melting point of Parylene C (290 ºC) (Harder et al. 2002) will not alter the mechanical flexibility of the material. The DC resistances of the samples are measured before and after bonding with no significant change observed (Table 3), confirming the ductility and durability of metal traces. Stretching marks and Parylene cracks are found along the folding line after thermal treatment, which is caused by stress concentration during folding. Additional Parylene coating can be performed after thermal bonding to conformally cover these cracks in order to ensure a good sealing for final

is due to the lack of control with the hand alignment.

Table 2. Design specifications of two fold-and-bond coils.

suturing holes.

devices.

Fig. 12. Devices after thermal bonding: (a) Fold-and-bond coils after thermal bonding. (b) Overlapping metal wires with misalignments of 10 µm to 30 µm.

Fig. 13. (a) Demonstration of device's flexibility; (b) Stretching marks along the folding line.

The electrical characteristics of the fabricated fold-and-bond coils are studied before and after thermal bonding. The lump parameters are extracted from the same 3-element model, as summarized in Table 3. As expected, the self-inductance and Q-factor of the coil are increased by more than 90% for both coil designs after folding. Changing the wire width has no significant impact on the parasitic capacitance, indicating the capacitance between adjacent layers is dominant over the capacitance between turns. Coil prototype I shows a much higher ESR compared to its theoretical value (29 Ω), which may be attributed to the non-uniformity of metal thickness. Overall, the measured values show good agreement with the theory predictions, demonstrating that the theoretical model can predict the coil properties effectively.


Table 3. Measured electrical parameters of fold-and-bond coils using the 3-element model.

Implantable Parylene MEMS RF Coil for Epiretinal Prostheses 17

Fig. 16. The power transfer efficiency of difference devices vs. the separation distance of the

functions of the separation distance between the coil pairs. For comparisons, theoretical data are also studied based on the models discussed elsewhere (Ko et al., 1977), which match the testing results within a reasonable range. As expected, the coil prototype II with higher selfinductance and Q factor exhibits higher power transfer efficiency at the same separation distances. The power transfer efficiencies at different operation frequencies have also been investigated, as plotted in Fig.16. The results show that the power transfer efficiency can be enhanced by more than 3 times when the operation frequency is changed from ~1 MHz to ~2 MHz. This can be attributed to the effective Q factor increases by almost two times as the

coil pair.

frequency goes up.

To study the power transfer efficacy, the fabricated devices are tested using a simplified inductive link, as shown in Fig. 14. In this setup, the transmitter coil is hand-wound with a self-inductance of ~ 23 µH and a series resistance of ~ 1.5 Ω. The inner diameter of the transmitter coil is optimized to be ~ 30 mm (Ko et al., 1977). The receiver coil is the fold-andbond coil presented in Fig. 12. During the measurements, the primary stage is driven by an HP E3630A function generator with a sinusoidal input signal of 20 V peak to peak. Both the primary and secondary circuits are subject to parallel resonance with the same resonant frequencies of ~ 1 MHz. To minimize environmental interferences, both the transmitter and receiver coils are covered with aluminum foils as electromagnetic shielding.

Fig. 14. Experimental setup of power transmission measurement and its circuit diagram.

Preliminary experiments have been performed. A 10 Ω series resistor (Rs) is incorporated in the primary stage to monitor the output current from the amplifier. The voltage across the transmitter coil is then calculated by subtracting the resistor voltage from the output voltage of the amplifier. The transferred power, which is defined as the power delivered to a 1 kΩ load resistor (Rload), can be obtained by directly measuring the voltage across the load resistor. The power transfer efficiency of two coil prototypes, which is calculated as the ratio of the transferred power to the total output power from the amplifier, is plotted in Fig. 15, as

Fig. 15. Power transfer efficiencies of the fold-and-bond coils at 1 MHz, as functions of separation distances of the coil pair.

To study the power transfer efficacy, the fabricated devices are tested using a simplified inductive link, as shown in Fig. 14. In this setup, the transmitter coil is hand-wound with a self-inductance of ~ 23 µH and a series resistance of ~ 1.5 Ω. The inner diameter of the transmitter coil is optimized to be ~ 30 mm (Ko et al., 1977). The receiver coil is the fold-andbond coil presented in Fig. 12. During the measurements, the primary stage is driven by an HP E3630A function generator with a sinusoidal input signal of 20 V peak to peak. Both the primary and secondary circuits are subject to parallel resonance with the same resonant frequencies of ~ 1 MHz. To minimize environmental interferences, both the transmitter and

receiver coils are covered with aluminum foils as electromagnetic shielding.

Fig. 14. Experimental setup of power transmission measurement and its circuit diagram.

Fig. 15. Power transfer efficiencies of the fold-and-bond coils at 1 MHz, as functions of

separation distances of the coil pair.

Preliminary experiments have been performed. A 10 Ω series resistor (Rs) is incorporated in the primary stage to monitor the output current from the amplifier. The voltage across the transmitter coil is then calculated by subtracting the resistor voltage from the output voltage of the amplifier. The transferred power, which is defined as the power delivered to a 1 kΩ load resistor (Rload), can be obtained by directly measuring the voltage across the load resistor. The power transfer efficiency of two coil prototypes, which is calculated as the ratio of the transferred power to the total output power from the amplifier, is plotted in Fig. 15, as

Fig. 16. The power transfer efficiency of difference devices vs. the separation distance of the

coil pair.

functions of the separation distance between the coil pairs. For comparisons, theoretical data are also studied based on the models discussed elsewhere (Ko et al., 1977), which match the testing results within a reasonable range. As expected, the coil prototype II with higher selfinductance and Q factor exhibits higher power transfer efficiency at the same separation distances. The power transfer efficiencies at different operation frequencies have also been investigated, as plotted in Fig.16. The results show that the power transfer efficiency can be enhanced by more than 3 times when the operation frequency is changed from ~1 MHz to ~2 MHz. This can be attributed to the effective Q factor increases by almost two times as the frequency goes up.

Implantable Parylene MEMS RF Coil for Epiretinal Prostheses 19

factor of approximately 10. While direct fabrication could be too complicated to be carried out, the fold-and-bond technology has proven itself as a very promising fabrication technology. Although specifically tailored to the needs of retinal prostheses, because our coils are fully micromachined in a way compatible with multielectrode arrays and the Parylene-based embedded chip packages, these devices can be easily integrated with various system components to achieve a new range of true system solutions for both

This work is supported in part by the Engineering Research Center Program of the National Science Foundation under Award Number EEC-0310723 and by a fellowship from the Whitaker Foundation (D.R.). The authors would like to acknowledge Dr. Yang Zhi for his supports on the coil testing. We also want to thank Mr. Trevor Roper, Dr. Wen-Cheng Kuo, and other members at the Caltech Micromachining Laboratory for assistance with device

Artificial Retina Project. (2007). Retinal Diseases: Age-Related Macular Degeneration and

Bennett, J.; Tanabe, T.; D. Zeng, Sun, Y.; Kjeldbye, H.; Gouras, P. & Maguire, A.M. (1996).

Therapy. *Nature Medicine*, Vol. 2, (June 1996), pp. 649-654, ISSN 1078-8956. Chen, P.J.; Kuo, W.C.; Li, W. & Tai, Y.C. (2006) Q-enhanced Fold-and-bond MEMS

Dwight, H.B. (1945). *Electrical Coils and Conductors*, McGraw-Hill, ASIN B0007IT6Z0, New

Harder, T.; Yao, T.J.; He, Q.; Shih, C. Y. & Tai, Y.C. (2002). Residual Stress in Thin-film

Horch K.W. & Dhillon, G.S. (2004). *Neuroprosthetics Theory and Practice (Series in* 

Humayun, M.S.; Propst, R.; Eugene de Juan Jr.; McCormick, K. & Hickingbotham, D. (1994).

ISBN 978-1-4244-1907-4, Sanya, Hainan Island, China, January 2008. Chow, A.Y.; Chow, V.Y.; Packo, K.H.; Pollack, J.S.; Peyman, G.A. & Schuchard, R. (2006).

Photoreceptor Cell Rescue in Retinal Degeneration (RD) Mice by In Vivo Gene

Inductors. *Proc. IEEE Int. Conf. on Nano/Micro Engineered and Molecular Systems*,

The Artificial Silicon Retinamicrochip for the Treatment of Vision Loss from Retinitis Pigmentosa. *Arch Ophthalmol*, Vol. 122, (April 2004), pp. 460-469, ISSN

Parylene C. *Proc. IEEE Int. Conf. on Micro Electro Mechanical Systems*, ISBN 0-7803-

*Bioengineering & Biomedical Engineering-Vol.2)*, World Scientific Publishing

Bipolar Surface Electrical Stimulation of the Vertebrate Retina. *Arch Ophthalmol*,

biomedical and non-biomedical applications.

Retinitis Pigmentosa. Available from http://artificialretina.energy.gov/diseases.shtml.

7185-2, Las Vegas, United States, January 2002.

Vol. 112, (January 1994), pp. 110-116, ISSN 0003-9950.

Company, ISBN 9812380221, Singapore.

**6. Acknowledgment** 

simulation and fabrication.

0003-9950.

York, United States.

**7. References** 

Nevertheless, the power transfer efficiency of the current coil prototypes is still below 0.4% at the target implantation depth of ~ 15 mm, which is insufficient to drive electronics for high-density retinal stimulation. Whereas more power can be generated from the primary stage to compensate the low efficiency, the overheating issue of the coils becomes prominent. Therefore, future direction for coil optimization will mainly focus on increasing the number of metal layers to improve the Q factor. Theoretical evaluation predicts that at least 20 layers of metal will be required in order to achieve a reasonable Q factor of around 10, with a given gold thickness of ~ 2 µm.

#### **4.3 Challenges in packaging**

Device packaging for retinal prostheses presents several challenges. Electrical and fluidic isolation must be maintained to avoid device failures upon exposure to corrosive eye fluid. To ensure long-term use of implants, the interface between device and biological tissues should be stable and biocompatible in order to minimize inflammation and immune response. Packaging complication is also one of the significant challenges for high-density neural simulation/recording. Careful selection and evaluation of packaging materials and tools are necessary to address such challenges. We have studied the packaging performance of Parylene C using accelerated lifetime soak testing in heated saline. Preliminary results estimate that the lifetime of Parylene-coated metal at body temperature (37 °C) is more than 60 years, suggesting good packaging performance of Parylene C. Experimental details on Parylene packaging evaluation are discussed elsewhere (Li et al., 2010).

A chip-level integrated interconnect (CL-I2) packaging method has also been explored for integration of microcoils with CMOS integrated circuit (IC) chips and high-density prosthetic electrodes (Rodger et al., 2005 & Li et al. 2010). In this method, all the IC components necessary for a retinal implant can be embedded in silicon cavities and functional Parylene-based MEMS devices (e.g. microcoil and high-density electrode array) can then be fabricated on the same platform using the abovementioned Parylene-metal thin film technology. Chip-to-microdevice interconnections can be constructed using standard microfabrication techniques such as photolithography and metal etching; therefore, eliminating wire-bonding, bump-bonding, or soldering steps. Whereas initial experiments show promising results, continuous investigations will be necessary to collect more data in order to optimize integration process and to further refine our knowledge of Parylene packaging behavior.

#### **5. Conclusion**

In this work, various types of MEMS coils have been designed and fabricated using the Parylene-metal-Parylene skin technology. Experiments have been performed to measure the electrical properties of the coils and the results show good agreement with the theoretical values. The data transfer effect has been successfully demonstrated with the telemetry link setup. However, the power transfer efficiency at the separation distance of 15 mm is below 0.4%, which is relatively low for high-density retinal stimulation. Given the constraints of device geometries, it is believed that increasing the number of metal layers will be the most effective and applicable way to enhance the Q factor of microcoils. According to the analytical models, at least 20 layers of metal will be needed in order to achieve a coil Q factor of approximately 10. While direct fabrication could be too complicated to be carried out, the fold-and-bond technology has proven itself as a very promising fabrication technology. Although specifically tailored to the needs of retinal prostheses, because our coils are fully micromachined in a way compatible with multielectrode arrays and the Parylene-based embedded chip packages, these devices can be easily integrated with various system components to achieve a new range of true system solutions for both biomedical and non-biomedical applications.

#### **6. Acknowledgment**

18 Microelectromechanical Systems and Devices

Nevertheless, the power transfer efficiency of the current coil prototypes is still below 0.4% at the target implantation depth of ~ 15 mm, which is insufficient to drive electronics for high-density retinal stimulation. Whereas more power can be generated from the primary stage to compensate the low efficiency, the overheating issue of the coils becomes prominent. Therefore, future direction for coil optimization will mainly focus on increasing the number of metal layers to improve the Q factor. Theoretical evaluation predicts that at least 20 layers of metal will be required in order to achieve a reasonable Q factor of around

Device packaging for retinal prostheses presents several challenges. Electrical and fluidic isolation must be maintained to avoid device failures upon exposure to corrosive eye fluid. To ensure long-term use of implants, the interface between device and biological tissues should be stable and biocompatible in order to minimize inflammation and immune response. Packaging complication is also one of the significant challenges for high-density neural simulation/recording. Careful selection and evaluation of packaging materials and tools are necessary to address such challenges. We have studied the packaging performance of Parylene C using accelerated lifetime soak testing in heated saline. Preliminary results estimate that the lifetime of Parylene-coated metal at body temperature (37 °C) is more than 60 years, suggesting good packaging performance of Parylene C. Experimental details on

A chip-level integrated interconnect (CL-I2) packaging method has also been explored for integration of microcoils with CMOS integrated circuit (IC) chips and high-density prosthetic electrodes (Rodger et al., 2005 & Li et al. 2010). In this method, all the IC components necessary for a retinal implant can be embedded in silicon cavities and functional Parylene-based MEMS devices (e.g. microcoil and high-density electrode array) can then be fabricated on the same platform using the abovementioned Parylene-metal thin film technology. Chip-to-microdevice interconnections can be constructed using standard microfabrication techniques such as photolithography and metal etching; therefore, eliminating wire-bonding, bump-bonding, or soldering steps. Whereas initial experiments show promising results, continuous investigations will be necessary to collect more data in order to optimize integration process and to further refine our knowledge of Parylene

In this work, various types of MEMS coils have been designed and fabricated using the Parylene-metal-Parylene skin technology. Experiments have been performed to measure the electrical properties of the coils and the results show good agreement with the theoretical values. The data transfer effect has been successfully demonstrated with the telemetry link setup. However, the power transfer efficiency at the separation distance of 15 mm is below 0.4%, which is relatively low for high-density retinal stimulation. Given the constraints of device geometries, it is believed that increasing the number of metal layers will be the most effective and applicable way to enhance the Q factor of microcoils. According to the analytical models, at least 20 layers of metal will be needed in order to achieve a coil Q

Parylene packaging evaluation are discussed elsewhere (Li et al., 2010).

10, with a given gold thickness of ~ 2 µm.

**4.3 Challenges in packaging** 

packaging behavior.

**5. Conclusion** 

This work is supported in part by the Engineering Research Center Program of the National Science Foundation under Award Number EEC-0310723 and by a fellowship from the Whitaker Foundation (D.R.). The authors would like to acknowledge Dr. Yang Zhi for his supports on the coil testing. We also want to thank Mr. Trevor Roper, Dr. Wen-Cheng Kuo, and other members at the Caltech Micromachining Laboratory for assistance with device simulation and fabrication.

#### **7. References**

Artificial Retina Project. (2007). Retinal Diseases: Age-Related Macular Degeneration and Retinitis Pigmentosa. Available from

http://artificialretina.energy.gov/diseases.shtml.


Implantable Parylene MEMS RF Coil for Epiretinal Prostheses 21

Rizzo, J.F.; Wyatt, J.L.; Loewenstein, J.; Montezuma, S.; Shire, D.B.; Theogarajan, L. & Kelly,

Rizzo, J.F. (2011). Update on Retinal Prosthetic Research: The Boston Retinal Implant

Rodger, D. C.; Weiland, J. D.; Humayun, M. S. & Tai, Y.-C. (2005). Scalable Flexible Chip-

Rodger, D.C.; Weiland, J.D.; Humayun, M.S. & Tai, Y.C. (2006), Scalable High Lead-count

Rodger, D.C.; Fong, A.J.; Li, W.; Ameri, H.; Ahuja, A.K.; Gutierrez, C.; Lavrov, I.; Zhong, H.;

*Actuators B: Chemical*, Vol. 132, (June 2008), pp. 449-460, ISSN 0925- 4005. Stieglitz, T.; Haberer, W.; Lau, C. & Goertz, M. (2004). Development of an Inductively

Tropepe, V.; Coles, B.L.K.; Chiasson, B.J.; Horsford, D.J.; Elia, A.J.; Mclnnes, R.R. & Kooy,

Wong, Y.T.; Chen, S.C.; Seo, J.M.; Morley, J.W.; Lovell, N.H. & Suaning, G.J. (2009). Focal

Weiland J.D. & Humayun, M.S. (2008). Visual Prosthesis. *Proceedings of the IEEE*, Vol. 96,

World Health Organization. (2011). Prevention of Blindness and Visual Impairment. Available from http://www.who.int/blindness/causes/priority/en/index.html. Wu, C.; Tang, C. & Liu, S. (2003). Analysis of On-chip Spiral Inductors Using the Distributed

Wu J. (2003). *Inductive Links with Integrated Receiving Coils for MEMS and Implantable* 

*Applications* PhD thesis, University of Notre Dame. Available from http://etd.nd.edu/ETD-db/theses/available/etd-09302003-162720/.

*Meet.*, ISBN 0-7803-8439-3, San Francisco, CA, USA, September 2004. Tai, Y.C.; Rodger, D.C.; Li, W. & Tooker, A. (2006). *Method for Decreasing Chemical Diffusion in* 

*Ophthalmol*, Vol. 11, (June 1993), pp. 1460-1466, ISSN 0003-9950.

*Ophthalmol Vis. Sci.*, Vol. 45, pp. 3399.

0-7803-8994-8, Seoul, South Korea, June 2005.

(September 2006), pp. 107-114, ISSN 0925- 4005.

http://www.freepatentsonline.com/y2006/0255293.html

*Research,* Vol 49, (May 2009), pp. 825-833, ISSN 0042-6989.

(March 2000), pp. 2032-2036, ISSN 1934-7391.

(July 2008), pp. 1076-1084, ISSN 0018-9219.

11/408809. Available from

ISSN 0018-9200.

1070-8022.

Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa. *Arch* 

S.K. (2004). Development of a Wireless, Ab Externo Retinal Prosthesis. *Invest* 

Project. *Journal of Neuro-Ophthalmology,* Vol.32, (June 2011), pp. 160-168, ISSN

level Parylene Package for High Lead Count Retinal Prostheses. *Proceedings of the 13th International Conference on Solid-State Sensors, Actuators and Microsystems*, ISBN

Parylene Package for Retinal Prostheses. *Sensors and Actuators B: Chemical*, Vol. 117,

Menon, P.R.; Meng, E.; Burdick, J.W.; Roy, R.R.; Edgerton, V.R.; Weiland, J.D.; Humayun, M.S. & Tai, Y.C. (2008). Flexible Parylene-based Multielectrode Array Technology for High-density Neural Stimulation and Recording. *Sensors and* 

Coupled Epiretinal Vision Prosthesis. *Proc. Int. IEEE Eng. in Med. and Biol. Soc.* 

*Parylene and Trapping at Parylene-to-parylene Interfaces*, US Patent Applicatio

D.V.D. (2000). Retinal Stem Cells in the Adult Mammalian Eye. *Science*, Vol. 287,

Activation of the Feline Retina via a Suprachoroidal Electrode Array. *Vision* 

Capacitance Model. *IEEE J. of Solid-State Circuits*, Vol. 38, (June 2003), pp. 1040-1044,


Humayun, M.S.; Eugene de Juan Jr.; Weiland, J.D.; Dagnelie, G.; Katona, S.; Greenberg, R. &

Javaheri, M.; Hahn, D.S.; Lakhanpal, R.R.; Weiland, J.D. & Humayun, M.S. (2006). Retinal

Kim, S.Y.; Sadda, S.; Pearlman, J.; Humayun, M.S.; Eugene de Juan Jr. & Green, W.R.

Ko, W.H.; Liang, S.P. & Fung, C.D.F. (1977). Design of Radio-frequency Powered Coils for

Li, W.; Rodger, D.C.; Weiland, J.D; Humayun, M.S. & Tai, Y.C. (2005). Integrated Flexible

Li, W.; Rodger, D.C. & Tai, Y.C. (2008). Implantable RF-coiled Chip Packaging. *Proc. IEEE* 

Li, W.; Rodger, D. C.; Meng, E.; Weiland, J. D.; Humayun, M. S. & Tai, Y.-C. (2010) Wafer-

Licari J. J. & Hughes, L. A. (1990). *Handbook of Polymer Coating for Electronics: Chemistry,* 

MacLaren, R.E.; Pearson, R.A.; MacNeil, A.; Douglas, R.H.; Salt, T.E.; Akimoto, M.; Swaroop,

Meng E., Li P.Y. & Tai, Y.C. (2008) Plasma Removal of Parylene C, *Journal of Micromechanics and Microengineering,* Vol 18, (February 2008), pp. 045004, ISSN 1361-6439. Mokwa, W.; Goertz, M. C.; Krisch, K. I.; Trieu, H.-K. & Walter, P. (2008) Intraocular

Norton, E.W.D.; Marmor, M.F.; Clowes, D.D.; Gamel, J.W.; Barr, C.C.; Fielder, A.R.;

*IEEE-EMBS Conf.*, ISBN 0-7803-8741-4, Shanghai, China, January 2005. Li, W.; Rodger, D.C.; Meng, E.; Weiland, J.D.; Humayun, M.S. & Tai, Y.C. (2006). Flexible

*Research*, Vol. 39, (July 1999), pp. 2569-2576, ISSN 0042-6989.

ISSN 0304-4602.

ISSN 0140-0118.

January 2008.

0028-0836.

August 2008.

742, ISSN 1057-7157.

Park Ridge, New Jersey, United States.

Okinawa, Japan, May 2006.

0275-004X.

Suzuki, S. (1999). Pattern Electrical Stimulation of the Human Retina. *Vision* 

Prostheses for the Blind. *Ann Acad Med,* Vol. 35, (March 2006), pp. 137-144, 2006,

(2002). Morphometric Analysis of the Macula in Eyes with Disciform Age-realted Macular Degeneration. *Retina*, Vol. 22, No. 4, (August 2002), pp. 471-477, ISSN

Implant Instruments. *Med. Bio. Eng. Comput.*, Vol. 15, (November 1977), pp. 634-640,

Ocular Coil for Power and Data Transfer in Retinal Prostheses. *Proc.27th Ann. Int.* 

Parylene Packaged Intraocular Coil for Retinal Prostheses. *Proc. 4th Int. IEEE-EMBS Special Topic Conf. on Microtechnologies in Medicine and Biology*, ISBN 1-4244-0338-3,

*Int. Conf. on Micro Electro Mechanical System*, ISSN 1084-6999, Tucson, United States,

Level Parylene Packaging with Integrated RF Electronics for Wireless Retinal Prostheses. *Microelectromechanical Systems, Journal of*, Vol. 19, (June 2010) pp. 735-

*Technology, and Applications*, William Andrew Publishing/Noyes, ISBN 081551235X,

A.; Sowden, J.C. & Ali, R.R. (2006). Retinal Repair by Transplantation of Photoreceptor Precursors. *Nature*, Vol. 444, (November 2006), pp. 203-207, ISSN

Epiretinal Prosthesis to Restore Vision in Blind Humans. *Proc. 30th Ann. Int. IEEE EMBS Conf.*, ISBN 978-1-4244-1814-5, Vancouver, British Columbia, Canada,

Marshall, J.; Berson, E.L.; Rosner, B.; Sandberg, M.A.; Hayes, K.C.; Nicholson, B.W.; Weigel-DiFranco, C.; Willett, W.; Felix, J.S. & Laties, A.M. (1993). A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa. *Arch Ophthalmol*, Vol. 11, (June 1993), pp. 1460-1466, ISSN 0003-9950.


http://www.freepatentsonline.com/y2006/0255293.html


**2** 

*China* 

**MEMS-Based Microdevice for** 

**Cell Lysis and DNA Extraction** 

*State Key Lab. of Transducer Tech., Inst. of Electronics, Chinese Academy of Sciences* 

With the development of microelectromechanical system (MEMS) technology, micrototal analytical systems (μTAS) which has the potential for integrating sample pretreatment, target amplification, and detection, has been in progress. Micromachined analytical systems have several advantages over their large-scale counterparts, including low cost, disposability, low reagent and sample consumption, portability, and lower consumption. Many such devices have been demonstrated in the literature, including PCR microchips (Northrup et al., 1993; Copp et al., 1998; Panaro et al., 2005), DNA microchips (Fan et al., 1999), DNA biosensors (Kwakye et al., 2006), capillary electrophoresis (CE) microchips (Harrison et al., 1993; Backhouse et al., 2003; Liu et al., 2006), protein microchips (Yang et al., 2001; Wilson & Nie, 2006), etc. Most of these analytical processes need an effective yet simple method of obtaining high-quality DNA. Hence miniature devices for rapid sample pretreatment of DNA, including cell lysis and genomic DNA purification, are crucial for

Traditional phenol extraction is a complex and time-consuming method for extracting DNA, and even some commercial purification kits require several centrifugal operations. The implementation of DNA purification on a microdevice is initially demonstrated based on the principle of solid phase extraction (SPE). The SPE on-microdevice can minimize sample loss and contamination problems as well as reduce analysis time, and besides, this SPE method can avoid problems of physical and biochemical degradation of DNA. For example, Tian et al. (Tian et al., 2000) established an SPE DNA purification microdevice in a capillary packing with silica resin matrix which could extract enough DNA for PCR reaction. Wolfe et al. (Wolfe et al., 2002) and Breadmore et al. (Breadmore et al., 2003) immobilized bare-silica beads matrix in microchannels by sol–gel technology for DNA purification. But a high packing density for larger surface area in the microfluidic device results in problems of backpressure and clogging of crude samples, and what is more, it is difficult to control the small particles in microdevices. A micropillar array fabricated by MEMS technology in a microchamber or channel increases the surface area available for DNA adsorption (Christel et al., 1999; Cady et al., 2003). However, the increasing surface area is limited and the problems of clogging could not be completely solved. Hence, a novel solid-phase matrix

which should be easily integrated in microdevices is under demand.

**1. Introduction** 

genetic application.

Xing Chen, Dafu Cui, Haoyuan Cai, Hui Li, Jianhai Sun and Lulu Zhang

