1、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, Mller, Fromherz, Biol. Cybern. 84, 239-249 (2001),Simple Ru
2、gged 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,MANUFA
3、CTURE,DATA,PROCESSES GROWTH,PROBLEMS,Polyimide Picket Fences.,MANUFACTURE,Gnther 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 individu
4、al 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 accessedNeurons are mobile, thus repeated measurements ofa specific neuron are difficult,Micro-cages: each n
5、euron is trapped into one cage,Features:Arrays of neuro-cages to allow the formation of neural networksOne-to-one correspondence between neurons and electrodesNeurite growth is not affected by the physical confinement,Qing He., Ellis Meng, Yu-Chong Tai, Christopher M. Jerome Pine, etc, The 12th Inte
6、rnational Conference on Solid-State Sensors, Boston, MA, Jun 8-12, 2003,SILICON MICROMACHINED NEUROCHIPS,Neurochip: 1 cm square, 500 m thick silicon wafer, with a 4x4 array of wells spaced on 100 m centers,MICROFABRICATION PROCESS,Composite layer of 180 nm LPCVD silicon nitride on top of 50 nm therm
7、al oxide is formed Pattern nitride-oxide layer to define the openings for the metal electrodes 1 m oxide step around the electrode openings Nitride is stripped Metallization is done using lift-off process Metallization is covered by a composite insulation Layer of 0.5 m LTO and 1 m PECVD nitride Ope
8、ning of bonding pads and alignment marks EDP etching on the back using the boron-doped layer as an etch stop RIE is used to form grillwork Neuron wells are formed by EDP etching to the electrodes on the front side of the wafer Removal of pad oxide at the bottom of the wells,EXPERIMENTAL RESULTS,Neur
9、on sucked in pipette Cell ejected from pipette near a well Pusher used to move cell over the well Cell implanted in the well by means of the pusher,Conclusions:Survival rate of 75%: biocompatibility of the neurochipAction potentials arising from individual neuronsdetected with a signal-to-noise rati
10、o of 35-70:1 Drawbacks:Making bulk micromachined wells is very complicatedNeurites growing out on the top of the well tend to pullneuron away,PARYLENE NEURO-CAGES,Advantages of parylene:Non-toxic, extremely inert, resistant to moistureand most chemicals, and biocompatibleIts conformal deposition mak
11、es it easy to fabricate3D structures like neuro-cageIt is transparent: neurons can be seen through thecages,The cage consists of a top loading access hole, the cage body, and 6 thin channels for neurite overgrowth,MICROFABRICATION PROCESS,Oxide layer is grown on silicon wafer Channel height controll
12、ing sacrificial layer is patterned Two parylene and one photoresist layers are used toform the cage The sacrificial materials are removed to release themicrocage,To improve the adhesion of the cages to the substrate:Mechanically anchoring parylene to substrate using DRIETo roughen the anchoring area
13、 with short time etching in BrF3 or XeF2,PARYLENE-TO-OXIDE ADHESION,EXPERIMENTAL RESULTS,Conclusions:Parylene has been shown to be biocompatibleThe parylene neurocages are mechanicallyfunctional,BUILDING LIVING NEURON CHIP WITH PA GELS,replica molding,replica molded microwells,Poly(dimethylsiloxane)
14、 Substrates,PEPTIDE AMPHIPHILE,Hartgerink, J.D., E. Beniash, and S.I. Stupp, Science, 2001. 294(5547): p. 1684-1688.,PDMS,MEMBRANE PATTERNING,SU8-2025 Separation layer,PDMS membrane layer,Bulk PDMS,SELF REGISTRATED MEMBRANE PATTERNING,Professor Horacio D. Espinosa TA: Yong Zhu Team members,ACKNOWLEDGEMENT,
