“Detection , Stimulation, and Inhibition of Neuronal Signals with High Density Nanowire Transistor Arrays” By Fernando Patolsky Science: August 2006OutlineNeuronNW-FETs & NeuronsFabricationStimuli PropagationAxon-End Signal BlockingMulti-Neurite StructuresConclusionCurrent MethodsNeuron ExcitationErika A. ParraEE2354/9/07Neuron TerminologyNW-FET & NeuronsDevice FabricationResults•Signal Propagation•Signal Blocking•Multi-Neurite StructuresConclusionsSoma – 3 to 18 umDendrites – cellular extensions, <1um thickAxon – cable-like projection, can be >1m, also <1um thickAxon terminalIC = intracellular1. Resting State ~ -70mV2. Depolarization3. RepolarizationNa++K+Na+++++Cell Action Potential• Potential outside of cell (by NW) becomes more negative (mirror image)• Accumulation of carriers at NW• P-type NW conductance enhanced++1. SiNW (20um) growth via CVD with Au cluster2. Diborane (B2H6) CVD for doping (p-type)3. Alignment through flow-directed technique4. Patterned and deposited contacts for source and drain (Ni). Passivated contacts (Si3N4) to survive cell culture conditions5. Patterned 50um squares for cell body and 3um wide lines for axion and dendrite grown. Deposited polylysine for adhesion of and directed growth6. Cell culturing Yield - 90%OpticalNW ElementNW-Neuron ArraySoma stimulationSimultaneous axon and dendrite peak spreading measurement- newSuperimposed signals: • Peak reduction & temporal spreading in dendrite• Measured latency matches previously reported valuesNW3 StimulatedPeak amplitude decrease at 0.4VBack propagation signal to soma unaffected by increasing potentialAxon end signal blocking at 0.9V-Suggests action is localized Propagation speed comparable in both directions through axonaxonSpike propagation w/o IC electrodeSomaNW-AxonIntracellular15ms 0.5nANW4 not connectedBiphasic stimuli500us train widthSignal mapping tool with high spatial and temporal resolution (150 devices with 400nm interspacing)Inhibits or stops signal propagation while mapping signal flow to dendrites and axonsReproducibility of NW-cell devices for flexible real-time cellular assays for drug discovery and testing – 43 out of 50 working devices over 500um axonPossible interface for implanted devicesMicropipette electrodes•Intracellular and extracellular•Resolution of 100nm per pipette and 10um between pipettes•Difficult to multiplexFET arrays•10um and larger on edge and 10um between electrodes•Size limits neuron analysis – cannot look at individual axons or dendrites500ms step of 0.1nATemporal correlationSoma initiated NW-Axon initiatedApplied biphasic potential1) 0.5V (successful 86%)2) 0.3V (below threshold) 3) 0.5V after TTX (toxin that blocks action
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