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BIO-MEMS DEVICES TO MONITOR NEURAL
ELECTRICAL CIRCUITRY
Andres Huertas, Michele Panico, Shuming Zhang
ME 381 Final Project, Dec 4th, 2003
OUTLINE
• Planar monitoring system
• Neurons cage array
• Living chips with peptide amphiphiles gels
ORIGINAL TECHNIQUE
•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.”
Jenker, Müller, Fromherz, Biol. Cybern. 84, 239-249 (2001)
PACKAGED CHIPS
MANUFACTURE
•Very simple design
•Scale is achievable
DATA
PROCESSES GROWTH
PROBLEMS
MANUFACTURE
Polyimide Picket Fences.
Günther Zeck and Peter, Fromherz, PNAS, 2001 vol. 98, no. 18, 10457-10462
MANUFACTURE
•Successful at
immobilizing neurons
•Retains Functionality
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 spaced
on 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 loading
access hole, the cage body, and
6 thin channels for neurite
overgrowth
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
PARYLENE-TO-OXIDE ADHESION
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
EXPERIMENTAL RESULTS
Conclusions:
• Parylene has been shown to be biocompatible
• The parylene neurocages are mechanically
functional
BUILDING LIVING NEURON CHIP WITH PA GELS
PA gels with trapped cells
Poly(dimethylsiloxane) Substrates
replica molding
photoresist
silicon
cast PDMS
replica molded microwells
PEPTIDE AMPHIPHILE
Hartgerink, J.D., E. Beniash,
and S.I. Stupp, Science, 2001.
294(5547): p. 1684-1688.
MEMBRANE PATTERNING
O2 Plasma
PDMS
SELF REGISTRATED MEMBRANE PATTERNING
SU8
SU8
SU8
SU8
SU8
SU8
SU8
SU8
Si
SU8-2025 Separation layer
PDMS membrane layer
Bulk PDMS
ACKNOWLEDGEMENT
• Professor Horacio D. Espinosa
• TA: Yong Zhu
• Team members