Rouschelecture.ppt

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

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

electrode array

transcranial interconnect

video encoder

signal processor

Information Transfer

electrode array

transcranial interconnect

signal processor

R.A.Normann et al.

Overview

Electrode Development: The neural interface

Polyimide electrode arrays Neural tissue engineering

Applications:Multi-channel neural

recording Intracortical microstimulation

Electrode Development:

“Building a better mouse trap”

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

signal/noiseratio

# neurons

electrode size

Parameter Space for Electrode Design

traditional efforts

Advanced

Neural

Engineering

traditional efforts

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**

Histology (Utah array)

Device Encapsulation0%

20%

100%

Excellent biocompatiblity

Excessive reactions400 um

100 um

micromotion?

Future Electrode Designs

High specificity and S/N

Biologically integrated with nervous tissue

On-board signal processing/telemetry

Mechanically flexible/minimal micromotionCandidate material = POLYIMIDE

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**

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

Polyimide ProcessingExternal accessExternal access

‘can’

silicon wafer

electrode site traceconnector template

metallization

polyimide, 1st layer

polyimide, 2nd layer

Simplified Interconnect System

• Electrical access to implanted electrodes

• 12-pin Microtech connector

or

• 18-pin Omnetics connector

cable

traces

400 um

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

Inserting Flexible Structures

•More complex devices will require advanced MEMS insertion technologies

400 um

insertion force < buckling force

Bio-MEMS Insertion tools

silicon ‘knife’

Polyimide electrode cable

PEG, dissolving

Bio-MEMS Insertion tools

Applying the silicon ‘knife’

brain

polyimide cable

90° bends

bone

FLEXIBILITY AND SURGICAL ACCESS

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

‘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

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

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**

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

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

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

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

Applications:

Basic science supporting cortical neuroprosthesis

development

Multi-channel neural recording

Intracortical microstimulation (ICMS)

Maximizing information transfer from the brain

Arizona tungsten-wire array

Multi-channel Recording

Motor prosthesis

Neurophysiology - plasticity

Acute vs. Chronic

‘Traditional’ Implants

2x5 tungsten microwire implant

Auditory cortex

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

*

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

3D views of the same data

Data Visualization

Intracortical Microstimulation (ICMS)

Maximizing information transfer to the brain

Sensory prosthesis

Basic neuroscience

behaving subjectelectrode array

Rat Auditory Detection

start toneno tone

food

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

ICMS

switches

Time (msec)

Current level (uAmps)

Parameters:150 usec pulse width100 Hz200 msec train duration1-100 uAmps

stimulus waveshape

Single electrode

ICMS

Rat Auditory Detection w/ICMS

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

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?

Conclusions

Advanced Neural

Interfaces

Basic Neuroscience

Applied Neuroprosthetics

Bioengineering Technology

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

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

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

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: