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[资源] INTEGRATED RETINAL IMPLANTS

INTEGRATED RETINAL IMPLANTS
Thesis by
Wen Li
In Partial Fulfillment of the Requirement
for the Degree of
Doctor of Philosophy
CALIFORNIA INSTITUTE OF TECHNOLOGY
Pasadena, California
2009
(Defended October 8, 2008)
© 2009
Wen Li
All Rights Reserved
ABSTRACT
Integrated wireless implants have always been the ultimate goal for neural
prostheses. However, technologies are still in development and few have actually been
transferred to clinical practice due to constraints in material biocompatibility, device
miniaturization and flexibility. In this dissertation, emphasis is placed on the development
of Parylene devices for neural prostheses, and particularly, for retinal prostheses that
partially restore lost vision for patients suffering from outer retina degeneration.
A basic Parylene-metal-Parylene skin technology for making planar Parylene
micro-electro-mechanical systems (MEMS) devices, such as electrode arrays and radiofrequency
(RF) coil, is first discussed, followed by accelerated lifetime soaking tests to
investigate the long term stability of such skins in hot saline under both passive and active
electrical stressing. Discussion is further expanded on a detailed description of the design,
fabrication, and testing procedure of two types of MEMS coils, which serve as receiver
coils for wireless power and data transfer in a retinal implant system. After that, an
embedded chip integration technology is presented, which allows the integration of
complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC) chips with
other MEMS devices and discrete components so as to achieve high-level system
functionality. Finally, an integrated wireless neural stimulator is designed and successfully
fabricated using a test chip.

vii
TABLE OF CONTENTS
Acknowledgements ··············································································································· iv
Abstract ································································································································· vi
Table of contents ·················································································································· vii
List of illustrations ················································································································ xi
List of tables ························································································································ xix
Nomenclature ······················································································································· xx
Chapter 1 Introduction ······································································································ 1
1.1 Outer retinal diseases ··································································································· 1
1.2 Artificial visual prostheses for AMD and RP treatments ············································· 3
1.2.1 Introduction to visual prostheses ........................................................................ 3
1.2.2 State-of-the-art for epiretinal prostheses .......................................................... 10
1.2.3 Technical challenges of advanced epiretinal prostheses .................................. 12
1.3 Parylene-based MEMS technologies ········································································· 13
1.3.1 Introduction to MEMS ...................................................................................... 13
1.3.2 Introduction to Parylene C ................................................................................ 16
1.3.3 Parylene-based MEMS for neural prostheses .................................................. 19
1.4 Goal and layout of the dissertation ············································································· 21
1.5 Summary ···················································································································· 22
viii
Chapter 2 Parylene-metal-Parylene skin and its Long-term biostability ························ 23
2.1 Introduction ················································································································ 23
2.2 Parylene-metal-Parylene skin technology ·································································· 23
2.2.1 Review of flexible MEMS skin technologies .................................................. 23
2.2.2 Process development ......................................................................................... 25
2.2.3 Adhesion issue on interfaces............................................................................. 27
2.3 Interfacial adhesion enhanced process ······································································· 28
2.3.1 Accelerated-lifetime soaking test of Parylene bi-layer structures ................... 28
2.3.2 Water vapor permeation through thin-film Parylene C ................................... 32
2.3.3 Parylene heat molding ....................................................................................... 35
2.4 Accelerated-lifetime soaking test of Parylene-metal-Parylen skins ··························· 36
2.4.1 Sample preparation ........................................................................................... 36
2.4.2 Passive soaking test of Parylene-protected metal ............................................ 37
2.4.3 Active soaking test of Parylene-protected metal .............................................. 40
2.5 Summary ···················································································································· 45
Chapter 3 Design of Parylene-based mems coils···························································· 46
3.1 Introduction ················································································································ 46
3.2 Inductive link system overview ················································································· 46
3.3 Design of planar MEMS coils ···················································································· 49
3.3.1 Self-inductance .................................................................................................. 49
3.3.2 Effective series resistance ................................................................................. 50
ix
3.3.3 Parasitic capacitance ......................................................................................... 52
3.3.4 Self-resonant frequency and Quality factor ...................................................... 55
3.3.5 Simulation results .............................................................................................. 56
3.4 Inductive power link ·································································································· 58
3.5 Summary ···················································································································· 68
Chapter 4 Implantable MEMS RF coil for power and data trasmission ························· 69
4.1 Introduction ················································································································ 69
4.2 Planar MEMS RF coil ································································································ 69
4.2.1 Design and fabrication ...................................................................................... 69
4.2.2 Fabrication results ............................................................................................. 71
4.2.3 MEMS coil characteristics ................................................................................ 72
4.2.4 Data and power transfer measurements ............................................................ 75
4.3 Fold-and-bond MEMS coil ························································································ 77
4.3.1 Introduction ....................................................................................................... 77
4.3.2 Fabrication ......................................................................................................... 78
4.3.3 Fabrication and testing results .......................................................................... 81
4.4 Summary ···················································································································· 87
Chapter 5 Implantable RF-coiled chip integration technology ······································· 89
5.1 Introduction ················································································································ 89
5.2 Accelerated-lifetime soaking test of Parylene protected ICs ····································· 90
5.3 Integration demonstration ·························································································· 94
x
5.3.1 Design and fabrication ...................................................................................... 94
5.3.2 Fabrication and functional test results .............................................................. 99
5.4 Mechanical model for implantation studies ····························································· 101
5.5 Test chip system integration ····················································································· 108
5.5.1 Functional system prototype ........................................................................... 108
5.5.2 Fabrication of the assembled BION system ................................................... 110
5.5.3 Functional test of the assembled BION system ............................................. 115
5.5.4 Monolithic system processing ........................................................................ 118
5.6 Summary ·················································································································· 120
Appendix A: Dual-layer RF MEMS coil microfabrication process··································· 122
Appendix B: Fold-and-bond RF MEMS coil microfabrication process ···························· 128
Appendix C: Embedded chip integration microfabrication process ·································· 132
Bibliography ······················································································································· 143
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LIST OF ILLUSTRATIONS
Figure 1.1: (a) Normal vision. (b) Loss of central vision in patients with AMD. (c) Tunnel
vision in patients with RP. (Images courtesy of Artificial Retina Project) ............................. 2
Figure 1.2: Horizontal cross section through human eye and the cell layers in the retina.
(Eye illustrate adapted from Bausch & Lomb) ........................................................................ 3
Figure 1.3: Two commercially available neural prosthesis products: (a) A single channel
cochlear implant (Image adapted from Med-EL medical electronics). (b) A single channel
pacemaker. (Image adapted from Wikimedia Commons) ....................................................... 4
Figure 1.4: A blind patient with a cortical prosthesis system for over 20 years. The right
picture shows the implanted 64-electrode array. The wires are connected to electrodes
through a burr hole. ................................................................................................................... 5
Figure 1.5: Several types of microelectrodes for cortical prostheses: (a) Utah 100-channel
electrode array [17]. (b) Michigan 16-channel electrode array with flexible silicon ribbon
cable [18]. (c) Caltech 2-D 32-channel electrode array with flexible Parylene cable [19]. ... 5
Figure 1.6: Optical nerve prosthesis systems: (a) Approach used spiral cuff electrodes [20].
(b) “Hybrid retinal implant” approach [21]. ............................................................................ 7
Figure 1.7: Subretinal prostheses. (a) Schematic showing the location of the implants. (b)
The microphotodiode array made by Zrenner et al [24]. (c) The 5000 microphotodiode
array made by Chow et al [25]. ................................................................................................ 8
Figure 1.8: System overview of the epiretinal prosthesis. (Illustration courtesy of
NextGenLog) .......................................................................................................................... 10
xii
Figure 1.9: Several epiretinal implants: (a) Implanted Second Sight 16 electrode array [27].
(b) Retinal stimulator developed by Intelligent Medical Implants (Image adapted from
Intelligent Medical Implants). (c) Epiretinal stimulator made by the German team. (d) Test
platform of an epiretinal prosthesis system (Rizzo and Wyatt) (Image adapted from The
Boston Retinal Implant Project). ............................................................................................ 11
Figure 1.10: Illustration of bulk micromachining (A) and Bosch process (B). .................... 15
Figure 1.11: Illustration of surface micromachining. ............................................................ 15
Figure 1.12: Chemical structures of Parylene N, C, D, and HT, and some of the correlated
process parameters used in Parylene deposition system PDS 2010 and 2060. ..................... 17
Figure 1.13: Typical morphology of rabbit retinas after six month implantation. (Images
courtesy of Dr. Damien Rodger) ............................................................................................ 19
Figure 1.14: Parylene-based devices for neural prostheses: (a) cochlear probe; (b) 3-D
neural probe; (c) retinal multielectrode array; (d) spinal cord electrodes. ............................ 20
Figure 1.15: Proposed all-intraocular system for high density epiretinal implant. [35] ....... 21
Figure 2.1: Illustration of the flexible MEMS skin technology. ........................................... 24
Figure 2.2: Conceptual illustration of Parylene-metal-Parylene skins. ................................. 25
Figure 2.3: Fabrication process of Parylene-metal-Parylene skin technology. .................... 26
Figure 2.4: (a) Untreated Parylene bi-layer sample after one day soaking. Water bubbles
are formed at the interface. (b) Annealed Parylene-bi-layer sample after long-term soaking.
No delamination or water bubble is observed. ....................................................................... 28
Figure 2.5: Testing cells of Parylene bi-layer samples are placed in a convection oven. .... 30
xiii
Figure 2.6: Examples of Parylene heat molding: (left) Different shapes are formed for
Parylene films. (right) Demonstration of flexibility after heat molding. .............................. 35
Figure 2.7: A Parylene packaged thin film resistor with pure gold metallization. ............... 36
Figure 2.8: Microscope images of samples before and after passive ALSTs, showing
different corrosion mechanisms. ............................................................................................ 38
Figure 2.9: Simplified electrochemical test setup for active soaking test. A tested device is
shown in the right picture. ...................................................................................................... 41
Figure 2.10: Typical aging curve of a sample: (top) from sample set #3. (middle) from
sample set #6. (bottom) from sample set #9. ......................................................................... 41
Figure 2.11: Failure procedure observed in sample with 4.7 μm Parylene coating. ............ 42
Figure 2.12: Typical SEM images and EDS spectra on the top side and the back side of the
breakdown area. ...................................................................................................................... 43
Figure 2.13: Even bubbles observed on samples from set #9 after soaking in saline at 90 oC
for 65 days. .............................................................................................................................. 44
Figure 3.1: System configuration for the proposed system [64]. .......................................... 47
Figure 3.2: Average SAR for an average man exposed to 1mW/cm2 plane wave. (E
polarization denotes the electric field parallel to the body, H denotes the magnetic field
parallel to the body and K denotes the wave moving from head to toes or toes to head.) [70]
................................................................................................................................................. 49
Figure 3.3: Simplified representation of a circular planar MEMS coil. ................................ 49
Figure 3.4: Voltage profile of an n-turn planar coil. [74] ...................................................... 53
Figure 3.5: Voltage distribution of an N-layer coil. ............................................................... 54
xiv
Figure 3.6: Equivalent RLC circuit of a MEMS coil. ............................................................ 55
Figure 3.7: Simulated self-inductance and ESR of the sample coil. (Simulation courtesy of
Dr. Wen-Cheng Kuo.) ............................................................................................................ 58
Figure 3.8: Simulated self-inductances and ESR as functions of trace widths. The Qfactors
are summarized in the table. (Plots courtesy of Dr. Wen-Cheng Kuo.) .................. 58
Figure 3.9: System overview of an inductive power link for biomedical applications. The
secondary stage is modeled as a nonlinear circuit. ................................................................ 59
Figure 3.10: The secondary stage is simplified with an approximated linear model. .......... 59
Figure 3.11: Depiction of the inductive link, showing the size and relative position of the
transmitter coil and receiver coils. ......................................................................................... 63
Figure 3.12: Coupling coefficient as a function of coil separation (Transmitter coil ~ 30.8
mm in OD. Receiver coil ~ 9mm in OD). ............................................................................. 64
Figure 3.13: Analytical simulations of voltage gain (top) and power gain (bottom) as
functions of the receiver coil geometries. (n2 denotes the number of turns per layer.) ....... 66
Figure 3.14: Power delivered to the load, power dissipation and coil Q factors vs. number
of layers. (a) Coil with an inductance of 5.47 μH. (b) Coil with an inductance of 9.73 μH.
................................................................................................................................................. 68
Figure 4.1: Schematics of a dual-metal-layer MEMS coil. ................................................... 69
Figure 4.2: Detailed process of Parylene-based MEMS coil fabrication. ............................. 70
Figure 4.3: A fabricated ocular coil sitting on a penny. The right microscope image shows
the interconnection via between two layers of metals. .......................................................... 72
Figure 4.4: Demonstration of coil flexibility and foldability. ............................................... 72
xv
Figure 4.5: Equivalent RLC circuit of a MEMS coil. ............................................................ 73
Figure 4.6: Typical I-V curve of the Parylene-based coil. .................................................... 74
Figure 4.7: Coil impedance measurement and curve fitting using the 3-element model:
(right) Imaginary part; (left) Real part. (Data correspond to electrical parameters of coil in
Figure 4.3, s L = 1.19 μH, s R = 72 Ω and s C = 201 pF). ..................................................... 75
Figure 4.8: Schematic of the experimental setup for data transmission measurement.
(Images courtesy of Dr. Wentai Liu) ..................................................................................... 76
Figure 4.9: Inductive coupling test waveforms: (left) received signal is 25 mV peak to peak;
(right) received signal is 15 mV peak to peak. (Plots courtesy of Dr. Wentai Liu) ............. 76
Figure 4.10: Concept of fold-and-bond technology for Q-factor enhancement. A coil with
one fold is depicted for representation. .................................................................................. 78
Figure 4.11: (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. ............................ 79
Figure 4.12: Thermal bonding results of: (a) Sample annealed at 200 oC shows
delamination; (b) Good sample annealed at 250 oC. ............................................................. 80
Figure 4.13: Flexibility demonstration of the folded-and-bond devices. .............................. 81
Figure 4.14: Stretching marks along the folding line. ........................................................... 81
Figure 4.15: (a) Fold-and-bond coils after thermal bonding. (b) Overlapping metal wires
with misalignments of 10 μm to 30 μm. ................................................................................ 82
Figure 4.16: Q-factors as a function of frequencies. .............................................................. 84
Figure 4.17: Experimental setup for power transmission measurement. ............................. 85
xvi
Figure 4.18: Power transfer efficiency at 1 MHz vs. separation distance of the coil pair. ... 86
Figure 4.19: Power transfer efficiency vs. separation distance of the coil pair. ................... 87
Figure 5.1: Microscope images of chip metal pads. (a) A chip coated with annealed
Parylene C. (b) A chip with regular Parylene C after 6 months of soaking. (c) A bare chip
after 2 days of soaking. ........................................................................................................... 91
Figure 5.2: (left) Assembled RFID chip soaked in saline. (right) Close-up image of the
attached RFID chip. ................................................................................................................ 92
Figure 5.3: Test setup for the active soaking test of RFID chips. ......................................... 92
Figure 5.4: Active soaking test results of Parylene protected IC chips. ................................ 93
Figure 5.5: Parylene cracks is sample with (left) 11.7 μm Parylene coating and (right) 22.1
μm Parylene coating. .............................................................................................................. 94
Figure 5.6: Concept of embedded chip integration. .............................................................. 95
Figure 5.7: (left) EM 4100 RFID chip used to demonstrate the integration technology.
(right) WYKO image of a typical chip. ................................................................................. 95
Figure 5.8: Detailed process flow for embedded chip integration. ....................................... 97
Figure 5.9: Metal pole with a silicon piece for use to push the chip to the silicon shell. ..... 97
Figure 5.10: Vertical displacements of chips: 0μm step height indicates wafer level. ........ 98
Figure 5.11: (a) Example of <10 μm lateral misalignment of the chip; (b) Example of >10
μm lateral misalignment of the chip. ...................................................................................... 99
Figure 5.12: A fabricated device: (a) Overall view of the device. (b) Close-up view of the
embedded chip. (c) Close-up view of the coil wires. .......................................................... 100
Figure 5.13: Flexibility of the Parylene-metal-Parylene thin film. .................................... 100
xvii
Figure 5.14: Test setup to verify the function of embedded RFID chips. ........................... 101
Figure 5.15: Signal readout from the oscilloscope. ............................................................. 101
Figure 5.16: Prototype geometry for an all-intraocular Parylene-based device with all
required component regions for a completely implantable system. .................................... 103
Figure 5.17: Custom heat-forming mold. (Images courtesy of Dr. Damien Rodger) ........ 103
Figure 5.18: Two surgical models for acute implantation: model-I (a) is designed for test
chip integration; model-II (b) is designed for IRP1K integration. ...................................... 104
Figure 5.19: Example surgical photographs of prototype geometry implantation using (a)
test chip surgical model; and (b) IRP1K surgical model. .................................................... 105
Figure 5.20: Improved geometry for a completely implantable system. ............................ 106
Figure 5.21: Example of a coil with ACIOL haptics attached. ........................................... 106
Figure 5.22: Two surgical models for chronic implantation in canine eyes. ...................... 107
Figure 5.23: Surgical implantation photographs of improved surgical model under: (left)
anterior illumination, and (right) intravitreal illumination. ................................................. 107
Figure 5.24: BION chip layout and the pad connection. ..................................................... 109
Figure 5.25: Schematic overview of a BION chip integration system. ............................. 110
Figure 5.26: Fabrication process for the Parylene-based carrier substrate. Steps (b)-(d)
describe the lift-off technology for platinum patterning. ..................................................... 111
Figure 5.27: (left) Fabricated carrier substrate. (right) Parylene ribbons to hold the chip.
............................................................................................................................................... 112
Figure 5.28: A fabricated fold-and-bond coil with two layers of metal. The electrical
characteristics are measured and given in the table. ............................................................ 112
xviii
Figure 5.29: (a) A assembled BION system. (b) Interconnects formed with biocompatible
conductive silver epoxy: (left) coil contacts, (right) chip and capacitor contacts. .............. 113
Figure 5.30: Examples of chip interconnections. For the right sample, short circuit is
formed between adjacent pads. ............................................................................................ 114
Figure 5.31: A telemetry setup for functionality test of the assembled BION system. The
right picture shows a personal trainer and other peripheral accessories. ............................ 116
Figure 5.32: Typical simulation pulse measured from the electrode sites. ........................ 117
Figure 5.33: Waveforms of transferred voltage and current to the BION circuitry. ......... 117
Figure 5.34: Measured stimulating pulses (a), transferred voltages (b) and transferred
power (c) at different separation distances between two coils. ........................................... 118
Figure 5.35: Integration process for monolithic neural stimulator. ..................................... 119
Figure 5.36: Photoresist cracking and Parylene delamination encountered during the
monolithic integration processing. ....................................................................................... 120
xix
LIST OF TABLES
Table 1.1: Properties of Parylene N, C, D, HT, and PDMS. (Table adopted from [36]) ..... 17
Table 2.1: Samples preparation of Parylene bi-layers for soaking tests. .............................. 29
Table 2.2: Accelerated-lifetime soaking test results of Parylene bi-layer samples. Red color
denotes failed samples. Blue color denotes good samples. .................................................. 30
Table 2.3: Published WVTR data for Parylene C. (Courtesy of Parvathy Menon).............. 33
Table 2.4: Average WVTR of Parylene C thin films prepared under different conditions.
Each sample set contains 2 samples from a same batch of Parylene deposition. (Data
courtesy of Menon Parvathy[57].) ......................................................................................... 34
Table 2.5: Sample preparations. ............................................................................................. 37
Table 2.6: Soaking test results for Parylene-metal-Parylene structures under passive
conditions, and extrapolated data according to the Arrehnius relationship. ......................... 39
Table 3.1: Comparison of available power sources [64]. ...................................................... 47
Table 3.2: Design specifications of a sample coil. ................................................................ 57
Table 4.1: Design specifications of the fold-and-bond coils. ................................................ 82
Table 4.2: Extracted electrical parameters of fold-and-bond coils. ...................................... 83[ Last edited by yipddicorp on 2014-2-20 at 09:03 ]

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