Download - Rouschelecture.ppt
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Bio-MEMS: Designs and applications of cortical interfaces for neuroscience
and neuroprosthetics
Dr. Patrick J. RouscheAssistant Professor
Neural Engineering Device Development and Application Laboratories
Department of BioengineeringUniversity of Illinois at Chicago
Chicago, Illinois USA
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Neural Engineering
Challenges: 1) to develop a high-performance, long-lasting, 2-way interface with the central nervous system - ‘Bio-MEMS’
2) to understand the function and organization of the underlying neural circuitry - ‘Neurophysiology’
Goal: To create brain implant systems capable of increasing the quality of life for deaf, blind or paralyzed individuals - ‘Neuroprosthetics’
Technique: Multi-channel electrical stimulation or neural recording of the brain - ‘Information Transfer’
electrode array
transcranial interconnect
video encoder
signal processor
R.A.Normann et al.
Cortical Neuroprosthesis
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electrode array
transcranial interconnect
video encoder
signal processor
Information Transfer
electrode array
transcranial interconnect
signal processor
R.A.Normann et al.
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Overview
Electrode Development: The neural interface
Polyimide electrode arrays Neural tissue engineering
Applications:Multi-channel neural
recording Intracortical microstimulation
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Electrode Development:
“Building a better mouse trap”
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Neural Populations and Electrode Designs
scalp electrode
skin
bone
dura
dural electrode
skin
bone
dura
intracortical electrode
skin
bone
dura
intracellular electrode
skin
bone
dura
0.5 cm
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signal/noiseratio
# neurons
electrode size
Parameter Space for Electrode Design
traditional efforts
Advanced
Neural
Engineering
traditional efforts
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Current electrode designs
Arizona tungsten-wire array
poor geometrical site distribution
limited signal conditioning
limited long-term performance
Michigan silicon array
Utah silicon array
**US and European patents**
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Histology (Utah array)
Device Encapsulation0%
20%
100%
Excellent biocompatiblity
Excessive reactions400 um
100 um
micromotion?
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Future Electrode Designs
High specificity and S/N
Biologically integrated with nervous tissue
On-board signal processing/telemetry
Mechanically flexible/minimal micromotionCandidate material = POLYIMIDE
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Polyimide Electrode Structures
Single site (gold) 40 x 40 um
1.8 cm
Single shaft1000 x 160 x 10 um
Batch-fabricated on 4 inch Si wafers, mechanically flexible 2-dimensional devices
cable
Electrode shafts
Interconnect template
**US and European patents filed**
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Polyimide Electrode Structures
Bio-MEMS Advantages:• Mechanically flexible
• Custom-made device shapes
• Rapid prototyping
• Enhanced tissue integration
• Controllable surface chemistry
* Polyimide extends the design space of currently available multi-electrode array designs
500 um
200 um
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Polyimide ProcessingExternal accessExternal access
‘can’
silicon wafer
electrode site traceconnector template
metallization
polyimide, 1st layer
polyimide, 2nd layer
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Simplified Interconnect System
• Electrical access to implanted electrodes
• 12-pin Microtech connector
or
• 18-pin Omnetics connector
cable
traces
400 um
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Device Flexibility
2
2
e
crL
EIP
π=
- Material properties measured
- Calculated Euler’s buckling force = 0.224 g.
THEORETICAL
EXPERIMENTAL
- 5 devices ‘buckled’ against a microscale 5 times each
- Measured average buckling force = 0.3694 +- 0.0628 g
1 mm
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Inserting Flexible Structures
•More complex devices will require advanced MEMS insertion technologies
400 um
insertion force < buckling force
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Bio-MEMS Insertion tools
silicon ‘knife’
Polyimide electrode cable
PEG, dissolving
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Bio-MEMS Insertion tools
Applying the silicon ‘knife’
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brain
polyimide cable
90° bends
bone
FLEXIBILITY AND SURGICAL ACCESS
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Neural Recordings – single units
6 seconds
150
100
50
0
-50
-100
-150
units activated through whisker stimulation - 2 hours post-implant
0 2 4 6 8 10 12 14 16 18 20-80-60-40-200204060
uV
olt
s
msec
Expanded view of a doublet recorded 24 hours post-implant
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‘3-D’ Polyimide Structures
• 2-D planar devices are bent into 3-D structures
• increases insertion complexity (Bio-MEMS tools)
12-probe, 3 row 27-site device in 2-D form
1 mm
6-probe, 2 row, 12-site device ‘bent’ for implant
500 um
Via-holes for CSF perfusion
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Neural Tissue Engineering
Pro-actively enhancing or influencing the tissue-device interface through the biological modification of neural or supporting tissue or reactions
Encourage neuron growth into electrodes
Eliminate defensive encapsulation response
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Bioactive Polyimide Structures
micropipette polyimideelectrode
seededwell
NeuroTrace DiI tissue-labeling paste, inverted fluorescent microscope with rhodamine filter cube
1) Can electrodes be seeded?
cortical tissue
Confocal Microscopic Visualization **patent disclosure in progress**
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Non-Fluorescent
Fluorescent
NeuroTrace DiI tissue-labeling paste, inverted fluorescent microscope with FITC/rhodamine filter cube
2) Can gel remain in wells during implant?
4 hours, rat S1
Bioactive Polyimide Structures
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NeuroTrace DiI tissue-labeling paste, inverted fluorescent microscope with rhodamine filter cube
3) Will gel diffuse into neural tissue?
4 hours, rat S1
0
50
100
150
200
250
0
50
100
150
Distance (microns)
Pix
el V
alue
Bioactive Polyimide Structures
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NeuroTrace DiO tissue-labeling paste, confocal microscope with FITC/rhodamine filter cube
24 hours, rat S1
stained membranes?
4) Will membranes uptake the bioactive species?
Bioactive Polyimide Structures
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Captive-Neuron Biosensor
recording sites
amplifier 1) Culture a neural stem cell from the host
2) Put cell into chamber, verify interface
3) Implant chamber into host
4) Stem cell differentiates- extends through cage and becomes a bio-interface to neurons
**patent disclosure filed**
5 um
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Applications:
Basic science supporting cortical neuroprosthesis
development
Multi-channel neural recording
Intracortical microstimulation (ICMS)
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Maximizing information transfer from the brain
Arizona tungsten-wire array
Multi-channel Recording
Motor prosthesis
Neurophysiology - plasticity
Acute vs. Chronic
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‘Traditional’ Implants
2x5 tungsten microwire implant
Auditory cortex
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Arizona tungsten-wire array
Basic Neuroscience: Recording
800 usecs
= 100 uV
Neuron Waveshapes
0 0.1 0.2 0.3
0
20
40
Time (sec)
Sp
ike
s
TONE
Peri-StimulusTime Histograms
*
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0 0.02 0.04 0.06
0
10
20dsp002a
0 0.02 0.04 0.06
0102030
dsp002b
0 0.02 0.04 0.06
0
4
8dsp002c
0 0.02 0.04 0.06
0
2
4dsp008b
0 0.02 0.04 0.06
0
40
dsp010b
0 0.02 0.04 0.06Time (sec)
0
10
20dsp012b
0 0.02 0.04 0.06
0
10
20
dsp012c
0 0.02 0.04 0.06
0
4
dsp014a
0 0.02 0.04 0.06
0102030
dsp018a
0 0.02 0.04 0.06
0
40
dsp018b
0 0.02 0.04 0.06
0
40
80dsp018c
0 0.02 0.04 0.06Time (sec)
0
40
dsp018d
0 0.02 0.04 0.06
0
10
20
dsp020a
0 0.02 0.04 0.06
0
10
dsp024a
0 0.02 0.04 0.06
0
20
40dsp024b
0 0.02 0.04 0.06
0
0.4
0.8
Event003
Perievent Histograms, reference = Event003, bin = 1 ms
Counts/bin
Neural Firing Patterns
Multiple time-series representations
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3D views of the same data
Data Visualization
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Intracortical Microstimulation (ICMS)
Maximizing information transfer to the brain
Sensory prosthesis
Basic neuroscience
behaving subjectelectrode array
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Rat Auditory Detection
start toneno tone
food
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Characterizing Auditory Behavior
RICMS 11 Feb 25
0
20
40
60
80
100
0 20 40 60 80
Aud dB
% Dectected
Psychometric Function Curve
200+ trials
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ICMS
switches
Time (msec)
Current level (uAmps)
Parameters:150 usec pulse width100 Hz200 msec train duration1-100 uAmps
stimulus waveshape
Single electrode
ICMS
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Rat Auditory Detection w/ICMS
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Characterizing ICMS Behavior
RICMS11; Electrode 3; 3/30/01
0
20
40
60
80
100
0 20 40 60 80 100
Microamps
% Detected
200+ trials
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Psychometric Function Curves
0
20
40
60
80
100
0 20 40 60 80 100
MicroAmps
% D
etec
t9 electrodes, same subject
RICMS12, 8 elecs
0
20
40
60
80
100
0 20 40 60 80 100Microamps
% D
etec
ted
Ricms 11Ricms 12Ricms 13Ricms 14
Mean of 8 electrodes, 4 subjects• ICMS is an effective,
reproducible tool for the controlled transmission of information from the external world directly to the brain.
• What are the maximum information transfer limits?
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Conclusions
Advanced Neural
Interfaces
Basic Neuroscience
Applied Neuroprosthetics
Bioengineering Technology
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Future work
Electrode DevelopmentNSF
Applied NeuroprostheticsWhitaker
Applied Neuroscience/NeuroprostheticsNIH
Neurophysiological investigations of cortical plasticity
Information transfer limits using ICMS
Clinical trials to determine effective ICMS parameters in humans
Advanced interface design > nano-technologies
Polyimide electrode array development
Parametric studies of bio-integration techniques
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Acknowledgements
Dr. Daryl Kipke, Dr. David PivinDavid S. Pellinen, Justin Williams, Rio
Vetter, Mathew Holecko, Kereshmeh Shahari, Kevin Otto, Tim Becker
Arizona State University
Dr. Kenichi Yoshida, Aalborg U. - Denmark Dr. Richard A. Normann et al. - U. of Utah Dr. T. Stieglitz et al. Fraunhoffer Institute, GermanySociety for Neuroscience
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Electrode lead wires (exit brain) Brain tissue
Neurons
Glass ‘cone’
Dr. Phil Kennedy et al. Emory University
‘Cone’ filled with NGF
High performance (S/N)
Long-life (>700 days in humans!!) Growth
Low channel number!
Successful Tissue Integration
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Engineering Considerations
Safety
Multiple channels - 625?
Minimal tissue disruption – maintain function!
Extended life span - 30 years?
Manufacturing techniques
Stable interfacial contact - micromotion
For the neural interface: Signal encoding and
processing
Power management
Portability
Front-end transduction
Bandwidth
For the associated hardware: