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Neurochips a new way of Integration

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1 Neurochips a new way of Integration
MAN vs. MACHINE Neurochips a new way of Integration University of Waterloo - Analytical Instrumentation Chem Dr.Karanassios Annie Raditsis

2 building an interface that combines biology and technology
The Problem building an interface that combines biology and technology PROs Operates electrically, similar to the brain Computer = e- in a solid ion lattice Brain = ions in polar fluid Electrons within silicon have the mobility of 103 cm2/Vs (voltage*sec) (water within the brain = 10-3 cm2/Vs) CONs Lack of adaptability to change within computer versus the plasticity of the brain Functions are physically separate in a computer, while with a single piece of tissue can carry out a number of different functions The sizes of common biological electronics are too large to interface with ions (eg. pacemakers)

3 "Nervenzelle an Chip! Chip an Nervenzelle!"
Thanks to the Max Planck Institute for Biochemistry that took the step towards more specific biological-electronic communications with a device that allows a field effect transistor on a silicon chip to sense the electric potential created by a neuron, and the neuron to sense a voltage pulse in the chip. The Neurochip part-mechanical, part-living electronic circuit A Neurochip within a Perspex chamber Advantages: Neurochips have a smooth silicon finish, therefore increasing a neuron’s life span to years instead of 5-6 hours with previous technology The photoconductive property of silicon allows for less interference from resistance in conjunction with the neuron. This also betters the control of the frequency induced by experimenter The chip in general is of higher performance to specific functions with great speed and reliability

4 Here Is How It Is Done 1.The neuron
First, one isolates a neural network. A neural network within its own culture is known as a ganglia. Within the ganglia the neurons are connected by electrical synapses. The most common neuron used incorelation with the chip is a snail neuron – Lymnaea stagnalis A biological scheme of a typical neuron The treatment: 1. Soak brains is 25% lysterine 2. Additional soak in saline consisting of NaCl, KCl, MgCl2 and Hepes at pH 7.9 3. Fix onto a Sylgard dish containing antibiotic saline 4. Central ganglions are dissected 5. Then soak in antibiotic saline and pinned to a Sylgard dish 6. Remove outer sheath and soak in colgenase/dipase and trypsin 7. Treat with trypsin inhibitor 8. Apply a high-osmolarity medium based on glucose 9. The ganglia are opened with tungsten microneedle 10. Neurons are removed by suction through a micropipette 

5 2. The chip ► The Fabrication The Dimensions
4 x 4 array of neuron wells at the center a 9 mm long/ 3mm wide and 20µm thick silicon membrane. 2. The chip The Fabrication Starting with an epitaxy/silicon wafer (dia.100nm and resistance 2-4 Ω/cm) with a 16µm lightly-doped layer on to of a 4 µm heavily boron-doped. A composite layer of oxide/nitride insulator and thermal oxide is formed. The Photolithographic step – defines opening in the nitride/oxide layer for electrodes (c) The Plasma & Isotropic Silicon Etching step – etched into the nitride/oxide and silicon substrate The Semirecessed Process – creates a 1µm oxide step around the electrode opening Metallization – compensates for the stress acting on the chip during usage. Opening the Windows (at the Back of the Wafer) – open bonding pads and etch the alignment on the insulation layer. More Etching – having the alignment to be within 1 µm. Photolithographic steps and Etching on the Side of the Cavities - forms the grillwork in the heavily boron-doped layers There is also the fabrication of a picket fence made of polymers. It’s purpose is to restrict the movement of the isolated neuron.

6 growing out of the wells
3. Putting them together We left the neuron last in a micropipette they can now be implanted into the wells of the chip, through the grillwork. They are held to the chip by a capacitive stimulator and a recording transistor. The neuron sits on a gold electrode, which can be coated with platinum to lower the impedance. The neuron is placed in the well, creating the opportunity for growth. This growth occurs within the span of two days, until it forms a good seal with the bottom of the electrode. A live neural network growing out of the wells

7 4. Photoconductive Stimulation
For inducing firing onto a neuron, a narrow beam of light is directed at the specified neuron. The silicon interface of the chip possesses a photoconductive property. This allows the conductivity of the neuron to change. It is the act of change that induces the firing. 5. Synapses The firing results in an electric signal that travels across the synapse to communicate to adjacent neurons. This process is called Synapses. In essence the electric signal depolarizes the postsynaptic membrane of the neuron. This process in the basis on all neural communication and growth

8 6. Field Effect Transistors (FET)
A FET is a type of transistor that has the capability to amplify the humanly undetectable voltages that are produced by a single neuron. It creates an electric field, by supplying an electric charge to a metal plate attached to a battery and a semiconductor, thus drawing out electrons of an atom. The neuron’s ion current flows through the membrane, along a narrow gap between the neuron and the chip. The gap creates a voltage drop, which in turn changes the electron flow in the silicon on the opposite side of the insulating oxide layer. The net current is considered to be the Action Potential of the cell and appears only if the cell membrane is electrically inhomogeneous The resulting electric signal from synapses is the signal detected by the transistor. It then converts the signal into a voltage, in order to amply to a detectable level.

9 7. Neuroelectronic signal transmission
 First output is the burst of voltage pulses at the stimulator Second output is the intracellular voltage from within the neuron  Third is the extracellular voltage form the transistor The resulting voltage change can be expressed by the difference of the specific ion conductance in the attached and free membrane. The shapes of the postsynaptic records differ significantly from the intracellular voltages. This delay is distinct suggesting a role of differing chemicals within the neuron (eg. potassium channels)

10 So This is the fundamental step in neuro-manipulation, in its combination of culturing neurons on an inert surface of a microelectronically active substrate, isolating individual neurons without any disruption of migration, and noninvasive electronic interfacing for stimulation and recording These methods are suitable for long-term studies on synaptic modulation in small networks of invertebrate neurons that are connected by chemical synapses and contribute an astonishing amount to the world of science and technology. From the world of NASA NASA SCIENTISTS USE HANDS-OFF APPROACH TO LAND PASSENGER JET Imagine being able to land a jumbo jet without ever taking control of the stick. NASA scientists recently demonstrated the ability to control a 757 passenger jet simulation, using only human muscle-nerve signals linked to a computer. Neuroelectric control uses "neural net" software that "learns" patterns that can slowly change and evolve with time, as well as combining many patterns together to generate a response. October 2000 To the Medical World Severed optical nerves can be made to grow again   One of the most significant advances in nerve regeneration in a decade. After severing an optic nerve in rats, neurologists have found a way to reconnect it to the brain so that it once again transmits normal electrical signals. 05 December 01 Advanced within this field have only started to progress within the past 20 years and predictions are more advances as soon as the next 5 years

11 The Latest There has been development on a multi-neuron chip
This chip consist of two layers of 64 neurons, which have the ability of spiking neurons and dynamic synapses. Dynamic synapses provides a short-term plasticity (depression or facilitation). Therefore these neurons can be stimulated by an excitatory synapse, a depressing synapse and inhibitory synapse. Each layer has 63 excitatory neurons and 1 global inhibitory neuron. The excitatory neurons excite the global interneuron which in return, inhibits the excitatory neurons. Connections between the excitatory neurons can be configured It is a building block for a multi-chip spike- based system that can be used to explore spike-based models.

12 References Bonifazi, Paolo and Fromherz, Peter. Silicon Chip for Electronic Communication between Nerve Cells by Noninvasive Interfacing and Analog-Digital Processing. (2002) Jenkner, Martin. Muller, Bernt. And Fromherz, Peter. (2001) Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses. Vol. 84, # 4. pp Johnson, Colin. Neurochips detect brain’s reaction to learning. EE times. January 2, Locklear, Fred. Learning visualized in “neurochips’ December, 12, 2001 Max Planck Institute for Biochemistry, Department of Membrane and Neurophysics. Neuroelectronic Interfacing: Semiconductor Chips with Ion Channels, Nerve Cells and Brain. Berlin Neurochips Detect Brain’s Reaction to Learning. Vedantam, Shankar. Brain Cells, Silicon Chips Are Linked Electronically. Wastingon Post. Tuesday, August 28, pp.A03

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