BIO-MEMS DEVICES TO MONITOR NEURAL ELECTRICAL CIRCUITRY

Andres Huertas, Michele Panico, Shuming Zhang

ME 381 Final Project, Dec 4th, 2003

• Planar monitoring system

• Neurons cage array

• Living chips with peptide amphiphiles gels

OUTLINE

Jenker, Müller, Fromherz, Biol. Cybern. 84, 239-249 (2001)

•Simple

•Rugged

•Easiest solution

“Future hybrid neuron-semiconductor chips will consist of complex neural networks that are directly interfaced to electronic integrated circuits. . . and may lead to novel computational facilities.”

ORIGINAL TECHNIQUE

PACKAGED CHIPS

•Very simple design

•Scale is achievable

MANUFACTURE

DATA

PROCESSES GROWTH

PROBLEMS

Polyimide Picket Fences.

MANUFACTURE

Günther Zeck and Peter, Fromherz, PNAS, 2001 vol. 98, no. 18, 10457-10462

•Successful at immobilizing neurons

•Retains Functionality

MANUFACTURE

DATA

NEURO-CAGES FOR LIVE NEURAL NETWORKS STUDY

To study neural networks of individual neurons is the aim of neuroscience

Conventional technique: planar arrays of extracellular metal electrodes on which neural cultures are grown

Limitations:• Small proportion of neurons can be accessed• Neurons are mobile, thus repeated measurements of a specific neuron are difficult

Micro-cages: each neuron is trapped into one cage

Features:• Arrays of neuro-cages to allow the formation of neural networks• One-to-one correspondence between neurons and electrodes• Neurite growth is not affected by the physical confinement

Qing He., Ellis Meng, Yu-Chong Tai, Christopher M. Jerome Pine, etc, The 12th International Conference on Solid-State Sensors, Boston, MA, Jun 8-12, 2003

SILICON MICROMACHINED NEUROCHIPS

Neurochip: 1 cm square,500 µm thick silicon wafer, with a 4x4 array of wells spacedon 100 µm centers

MICROFABRICATION PROCESS

1) Composite layer of 180 nm LPCVD silicon nitride

on top of 50 nm thermal oxide is formed

2) Pattern nitride-oxide layer to define the openings

for the metal electrodes

3) 1 µm oxide step around the electrode openings

4) Nitride is stripped

5) Metallization is done using lift-off process

6) Metallization is covered by a composite insulation

Layer of 0.5 µm LTO and 1 µm PECVD nitride

7) Opening of bonding pads and alignment marks

8) EDP etching on the back using the boron-doped

layer as an etch stop

9) RIE is used to form grillwork

10) Neuron wells are formed by EDP etching to the

electrodes on the front side of the wafer

11) Removal of pad oxide at the bottom of the wells

EXPERIMENTAL RESULTS

a) Neuron sucked in pipette

b) Cell ejected from pipette

near a well

c) Pusher used to move cell

over the well

d) Cell implanted in the well

by means of the pusher

Conclusions:

• Survival rate of 75%: biocompatibility of the neurochip

• Action potentials arising from individual neurons

detected with a signal-to-noise ratio of 35-70:1

Drawbacks:

• Making bulk micromachined wells is very complicated

• Neurites growing out on the top of the well tend to pull

neuron away

PARYLENE NEURO-CAGES

Advantages of parylene:

• Non-toxic, extremely inert, resistant to moisture

and most chemicals, and biocompatible

• Its conformal deposition makes it easy to fabricate

3D structures like neuro-cage

• It is transparent: neurons can be seen through the

cages

The cage consists of a top loadingaccess hole, the cage body, and6 thin channels for neuriteovergrowth

MICROFABRICATION PROCESS

1) Oxide layer is grown on silicon wafer

2) Channel height controlling sacrificial layer is patterned

3) Two parylene and one photoresist layers are used to

form the cage

4) The sacrificial materials are removed to release the

microcage

To improve the adhesion of the cages to the substrate:

• Mechanically anchoring parylene to substrate using DRIE

• To roughen the anchoring area with short time etching in BrF3 or XeF2

PARYLENE-TO-OXIDE ADHESION

EXPERIMENTAL RESULTS

Conclusions:

• Parylene has been shown to be biocompatible

• The parylene neurocages are mechanically

functional

PA gels with trapped cells

BUILDING LIVING NEURON CHIP WITH PA GELS

silicon

photoresist

cast PDMS

replica molding replica molded microwells

Poly(dimethylsiloxane) Substrates

PEPTIDE AMPHIPHILE

Hartgerink, J.D., E. Beniash, and S.I. Stupp, Science, 2001. 294(5547): p. 1684-1688.

PDMS

O2 Plasma

MEMBRANE PATTERNING

Si

SU8SU8 SU8 SU8 SU8 SU8 SU8SU8

SU8-2025 Separation layer

PDMS membrane layer

Bulk PDMS

SELF REGISTRATED MEMBRANE PATTERNING

• Professor Horacio D. Espinosa

• TA: Yong Zhu

• Team members

ACKNOWLEDGEMENT