PURDUE UNIVERSITY GRADUATE SCHOOL

Thesis Acceptance

This is to certify that the thesis prepared

By

Entitled

Complies with University regulations and meets the standards of the Graduate School for originality

and quality

For the degree of

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, Chair

Approved by Major Professor(s):

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Date of Graduate Program Head's Approval:

Ming-fang Wang

A Three-Dimensional Si-Based Microelectrode for Neural Recording

Doctor of Philosophy

B. Ziaie, Chair

S. Mohammadi

R. Bashir

P. Irazoqui

12/07/07

B. Ziaie

M. J. T. Smith

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A THREE-DIMENSIONAL SI-BASED MICROELECTRODE

FOR

NEURAL RECORDING

A Dissertation

Submitted to the Faculty

of

Purdue University

by

Ming-Fang Wang

In Partial Fulfillment of the

Requirements for the Degree

of

Doctor of Philosophy

December 2007

Purdue University

West Lafayette, Indiana

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33075222008

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To my parents, brother and sister for their encouragement and support

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ACKNOWLEDGMENTS

I would like to thank my advisor, Professor Babak Ziaie, for giving me the opportunity to work on this interesting project and providing me inspiration all these years. I also appreciate the other members in my doctoral committee, Professor Rashid Bashir, Professor Pedro Irazoqui and Professor Saeed Mohammadi for their help and advice on my thesis. Especially, I would like to express my gratitude to Professor Kevin Otto with his research assistant Julia M. Colby for their assistance in the neural recording.

I would like to thank the staff of Birck Nanotechnology Center at Purdue University for their help and assistance. I would also wish to thank the staff of NCF at University of Illinois at Chicago for assisting in DRIE and the staff of CNF at Cornell University for assisting in PECVD deposition. Many thanks to my fellow graduate students, Nithin Raghunathan, Hyunjoong Kim, Chulwoo Son, Amani Salim, Meng Zhang (now at University of Michigan), Henry Wei, especially thanks to Teimour Maleki and Zhenwen Ding, for their help and advice in the lab work. Besides, in this period I have the chance to know many new friends who let me feel easy to work in the cleanroom and they are Hao-Han Hsu, Dennis Lin, Xiaoguang Liu, Hasan Sharifi, Yang Sui, Yanqing Wu, Yi Xuan and Lin Yu. Finally I would like to express my gratitude to the National Institute of Health for providing finance support in this project.

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TABLE OF CONTENTS

Page

LIST OF TABLES....................................................................................................... vii LIST OF FIGURES..................................................................................................... viii ABSTRACT................................................................................................................ xv 1. INTRODUCTION.................................................................................................. 1 1.1 A Short Introduction to Brain and Nerve Electrophysiology.......... 3 1.2 Metal-Electrolyte System and Conventional Microelectrodes........ 8

1.3 Advanced Microelectrodes by Microfabricated Technology........... 10 1.4 The Tetrode Technique for Neural Recording............................... 13 1.5 Overview of This Work................................................................. 15 2. THREE-DIMENSIONAL TECHNOLOGIES AND THEIR KEY PROCESSES….18 2.1 The Key Processes for 3-D Microfabricated Sensors.............................20 2.1.1 Photolithography on nonplanar surface............................ 22 2.1.2 Non-conventional etching technology.............................. 26 2.1.3 Thin and thick film deposition..........................................30 2.2 Review of Out-Of-Plane Structure Approaches.....................................31 2.2.1 Out-of-plane structure based on rotatable hinge............... 32 2.2.2 Out-of-plane structure based on surface tension force...... 33 2.2.3 Out-of-plane structure based on magnetic force............... 37 2.2.4 Out-of-plane structure based on material strain force....... 39 2.3 Conclusions.............................................................................................41 3. 3-D MICROSTRUCTURE FABRICATION BY THERMAL SHRINKAGE OF

COMPOSITE POLYIMIDE-OXIDE IN V-GROOVE JOINTS.............................43 3.1 The Typical Properties of Polyimide.................................................... 44 3.2 Theories of Bending Angle in V-grooves Joint and Their

Simulations......................................................................................... 46

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3.3 The Fabrication of V-groove Joints Filled with Polyimide.................. 56 3.4 The Mechanical Property of A Silicon Shank with V-groove

Joints................................................................................................... 61 3.5 Conclusions......................................................................................... 64 4. THE FABRICATION OF A THREE-DIMENSIONAL SI-BASED

MICROELECTRODE.......................................................................................... 65 4.1 Introduce The 3-D Microelectrode and Recording Sites

Configurations................................................................................... 65 4.2 Fabrication of the 3-D Microelectrode Based on Composite

Polyimide-Oxide in V-groove Joints....................................................73 4.2.1 V-groove joints created by KOH etching.........................73 4.2.2 Folding shank defined by DRIE……...............................75 4.2.3 Recording area prepared for the 3-D microelectrode.......77 4.2.4 Buried oxide removed by RIE………..............................79 4.2.5 Silicon dioxide passivation layer grown by wet

oxidation……………….……………………………...79 4.2.6 Metal deposition for interconnection, contact pad and

recording site..................................................................80 4.2.7 The composite passivation layer deposited by PECVD...83 4.2.8 HD-4010 polyimide coating in V-groove joints...............84 4.2.9 Passivation layer removed by RIE…................................85 4.2.10 Folding shank released by XeF2 etching.........................86 4.2.11 Shank folded with a post-curing process........................89 4.2.12 Recording site opening by wet etching...........................92 4.3 Failure Analysis in 3-D Microelectrode Fabrication......................... 93 4.3.1 Shank split after post-curing step….. ..............................93 4.3.2 Undesired etching attack on silicon shank.......................95 4.3.3 Asymmetric folding shanks..............................................95 4.3.4 Mechanical damage by tweezers or others.......................96 4.4 Conclusions......................................................................................... 98 5 MEASUREMENT AND EXPERIMENTAL RESULTS.................................... 99 5.1 The Yield of Metal Interconnection Through V-Groove..................... 99 5.2 Mechanical Strength of A 3-D Microelectrode................................. 104 5.3 The Microelectrode In Vitro Test.................................................... 109 5.4 The Microelectrode Package……..................................................... 112 5.5 Equivalent Circuit Model of Microelectrode……………………….. 113 5.6 Conclusions………………………………………………………… 116 6 CONCLUSIONS AND SUGGESTIONS FOR FURTHER RESEARCH..............118 REFERENCES.............................................................................................................. 126

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APPENDICES A. RUN SHEET FOR A 3-D MICROELECTRODE..................................................132 B. FABRICATION PROCESS FLOW FOR A 3-D MICROELECTRODE WITH

THROUGH-WAFER CONTACT PADS...............................................................134 VITA ...............................................................................................................................136

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LIST OF TABLES Table Page 2.1 The classification of photo resist coating methods......................................... 24 2.2 The classification of silicon etching methods................................................. 27 2.3 The surface tension force of several critical materials ................................... 34 2.4 The comparisons of several 3-D out-of-plane techniques .............................. 42 3.1 The critical properties of polyimide................................................................ 45

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LIST OF FIGURES Figure Page 1.1 The human brain, lateral view .......................................................................... 4 1.2 Structure of a typical neuron............................................................................. 5 1.3 Ionic composition of body electrolytes............................................................. 7 1.4 Action potential generated by a neuron ............................................................ 7 1.5 The schematic of electrical double layer formed at metal-electrolyte

interface and its equivalent circuit ................................................................... 8 1.6 Examples of early microelectrodes................................................................... 9 1.7 Micromachined silicon microprobes .............................................................. 10 1.8 A 3-D intracortical electrode array developed at the University of Utah

and Cyberkinetics Nanotechnology Systems, Inc.......................................... 11 1.9 Multi electrode array realized with LIGA method ......................................... 12 1.10 A 3-D active microelectrode developed at the University of Michigan ......... 13 1.11 Schematic of a tetrode surrounded by neurons in the brain............................ 14 1.12 The illustration of spike sorting from voltage signal recordings to measures

of association for three neural spike trains .................................................... 15 2.1 The milestone of major novel semiconductor devices invented..................... 19 2.2 The evolution of semiconductor sensor .......................................................... 19 2.3 An example for cantilever fabricated by micromachining ............................. 20 2.4 The schematic of a novel MOSFET and a 3-D microelectrode .................... 21 2.5 Schematic drawing of the resist behavior over deep and sharp structures ... 22

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2.6 Microscopic photos of photolithographic patterns at the nonplanar surface......................................................... .................................................. .24

2.7 SEM images of photo resist pattern across deep steps by spray coating

technique.................................... .................................................................... 25 2.8 SEM images of photo resist pattern across deep steps by electrodeposition

technique.................................... .................................................................... 26 2.9 SEM images of KOH etched silicon wafer oriented on (100) surface.............27 2.10 SEM images of a trench formed by DRIE etching........................................ . 28 2.11 SEM images of the patterns defined by DRIE etching....................................29 2.12 SEM images of XeF2 etching results....................................................... ....... 29 2.13 TEM/SEM images of thin film deposition results... ....................................... 31 2.14 SEM images of metal electroplating results.... ............................................... 31 2.15 The milestone of major out-of-plane techniques........................ .................... 32 2.16 The cross section view of a hinge during fabrication........................ ............. 33 2.17 (a) the SEM image of a hinge after rotation (b) the SEM image of robot legs realized with many Poly-Si hinges........................ ................................. 33

2.18 The simply process flow of out-of-plane structure based on surface tension

force rotation.................................................................................................. 35 2.19 (a) a digital image of multiple link assembly used surface tension force

technique (b) the relationship between bending angles and solder volume............................................................................................................ 36

2.20 (a) a microscopic photo of rugged silicon surface with porous structure

(b) a SEM image of rugged silicon surface with pillar structure which is modified from porous structure by an additional wet etching step.................37

2.21 Contact angle of regular macroporous silicon, macroporous silicon with

fractal-shape hierarchical structure, and fractal-shape hierarchical macroporous silicon after the wet etching step.............................................. 37

2.22 A schematic illustration of out-of-plane structure based on magnetic force

technique........................ ................................................................................ 38

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2.23 (a) SEM image of folded gold cantilever beams with electroplating

permalloy pieces (b) the measured results of bending angle versus external magnetic field relationship with a gold cantilever beam..................39

2.24 The process flow of a strain actuated folding structure........................ .......... 40 2.25 The SEM image of strain actuated folding structure........................ .............. 41 3.1 The HD-4010 polyimide test with a cross pattern........................ .................. 46 3.2 The thicknesses of polyimide HD-4000 series after film baked and cured

in terms of their spin coating rates................................................................. 46 3.3 The principle of rotation of V-groove joints filled with polyimide.................47 3.4 The rotation of V-grooves joint with a buried layer........................ ............... 48 3.5 The bending angle simulation results of a single V-groove joint....................52 3.6 The simulation results of the bending angle versus various linear shrinkage

percentages in a V-groove joint with and without the SiO2 buried layer...... 53 3.7 The comparisons of bending angle between formula and simulation results..54 3.8 The simulation results of bending angle with the assumption of 1-D and 2-D

polyimide shrinkage....................................................................................... 54 3.9 The simulation results of bending angle versus various thickness of SiO2

buried layer in a V-groove joint..................................................................... 55 3.10 The simulation results of bending angle in polyimide filled U-groove joint...56 3.11 Process flow for a 3-D structure fabrication........................ ........................... 57 3.12 Microscopic photo of an out-of-plane structure under fabrication..................57 3.13 SEM images of multi-shanks folded after polyimide cured at 350℃ for 2

hours. All the V-groove above are without a buried layer............................. 59

3.14 SEM images of multi-shanks folded after polyimide curing at 350℃ for 2

hours. All the V-groove above are with a buried layer.................................. 59

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3.15 The measurement of bending angle........................ ........................................ 60 3.16 The bending angle versus numbers of V-groove at temperature, 250℃,

300℃ and 350℃........................................................................................... 61 3.17 The distortion and stress distribution in a V-groove joints simulated by

Femlab after applied a force........................ .................................................. 62 3.18 The distortion and stress distribution in a silicon shank associated with a

V-groove joints simulated by Femlab after applied a force........................... 63 4.1 Schematic of the 3-D microelectrode........................ ..................................... 67 4.2 Three types of the recording site on the 3-D microelectrode........................ . 68 4.3 The illustration of V-groove region with metal interconnection passed

through 30μm depth........................ ............................................................... 68 4.4 Electrical potential distribution simulated by Femlab with cross-section

view................................................................................................................ 70 4.5 Electrical potential distribution simulated by Femlab with top view............. 71 4.6 Electrical potential distribution simulated by Femlab with a point charge

source located close to a tetrode recording site............. ................................ 72 4.7 Fabrication Process flow for the 3-D microelectrode........................ ............. 73 4.8 Anisotropic crystalline etching simulation (ACES) results

(RIE etching first)........................ .................................................................. 74 4.9 Anisotropic crystalline etching simulation (ACES) results

(KOH etching first)........................ ................................................................ 74 4.10 The V-groove created by KOH etching........................ .................................. 75 4.11 Microscopic photos of AZ 9260 photo resist pattern for DRIE mask.............76 4.12 SEM images of a 3-D microelectrode fabrication results after DRIE

etching............................................................................................................ 77 4.13 The recording area defined after metal deposited........................................... 78 4.14 SEM images of type I recording area definition............................................. 78

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4.15 SEM images on silicon shank after 2μm buried oxide removed by dry etching............................................................................................................ 79

4.16 Microscopic photos of the microfabricated electrode after wet oxidation......80 4.17 SEM images of photo resist patterns defined with dark film mask.................81 4.18 SEM images of a 3-D microelectrode after metal lift-off............................... 82 4.19 Microscopic photos of a 3-D microelectrode after a composite dielectric

layer deposited........................ ....................................................................... 84 4.20 Microscopic photos of a 3-D microelectrode after HD-4010 polyimide

coated........................ ..................................................................................... 85 4.21 Microscopic photos of a 3-D microelectrode after passivation layers etched

by RIE........................ .................................................................................... 86 4.22 Microscopic photos of a 3-D microelectrode covered with photo resist on

top and sidewall to protect from XeF2 etching........................ ...................... 87 4.23 Microscopic photos of V-groove joints experienced the XeF2 etching......... . 87 4.24 SEM images of a 3-D microelectrode after shanks released by XeF2

etching............................................................................................................ 88 4.25 Digital images of a 3-D microelectrode.......................................................... 89 4.26 Digital images of a 3-D microelectrode after shanks folded........................ .. 90 4.27 SEM images of a 3-D microelectrode after shanks folded completely...........90 4.28 Digital images of a 3-D microelectrode sitting on one cent coin.....................91 4.29 Digital images of a 3-D microelectrode after 2μm buried oxide underneath

the shanks removed by HF solution............................................................... 92 4.30 The recording sites are created after metal and passivation layers deposited,

lithography pattern defined and passivation layers etched........................ .... 93 4.31 Schematic of a shank split........................ ...................................................... 94 4.32 SEM images of a 3-D microelectrode experienced the shanks split............... 94 4.33 SEM images of the silicon shanks suffered attack by XeF2 etching...............95

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4.34 SEM images of a 3-D microelectrode undergone different bending angles

among four shanks........................ ................................................................. 96 4.35 SEM images of the V-groove joints after bending........................ ................. 96 4.36 Digital images of the 3-D microelectrode destroyed by external forces..........97 4.37 SEM images of the 3-D microelectrode destroyed by external forces............97 5.1 The metal interconnection through V-groove region is verified by applying

current (from 0 to 1mA) between contact pad and auxiliary pad and recording the voltage........................ ........................................................... 101

5.2 SEM image of metal interconnection deposited and patterned after

polyimide filled V-groove joints.................................................................. 101 5.3 The digital image of liquid metal filled in a small plastic pipe......................102 5.4 The schematic of metal interconnection passed through V-groove joint test

after the shank folded................................................................................... 103 5.5 The measurement of resistance of interconnection passed through

V-groove joints........................ .................................................................... 103 5.6 The measurement results of resistance of interconnection through

V-groove joints........................ .................................................................... 104 5.7 The set up for 3-D microelectrode mechanical test, including a syringe

pump, a strain gauge and a station........................ ....................................... 106 5.8 The strain gauge calibration relationship between measured voltage and

strain force........................ ........................................................................... 106 5.9 The digital image of 3-D microfabricated electrode penetrated into 1%

agarose gel........................ ........................................................................... 107 5.10 The insertion force recorded by strain gauge when microelectrode

penetrated into 1% agar gel........................ ................................................. 107 5.11 The digital images of microelectrode mechanical strength test.....................108 5.12 The maximum sustained force recorded by strain gauge when microelectrode

contacted with hard material........................................................................ 109 5.13 The electrical impedance measurement on the recording site of the shank...110

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5.14 Impedance values and phases in terms of frequencies........................ ......... 110 5.15 The schematic of in vitro recording of a 3-D microelectrode........................111 5.16 In vitro recording results from a 3-D microelectrode........................ ........... 111 5.17 The shank of a 3-D microelectrode inspected under microscope after

in vitro test........................ ........................................................................... 112 5.18 The microelectrode package........................ ................................................. 113 5.19 The equivalent circuit of a microelectrode........................ ........................... 113 5.20 The PSpice simulation results of in vitro recording which has input signal

(red line) and output signal (green line)........................ .............................. 116 6.1 The digital image of animal test........................ ........................................... 120 6.2 Schematic of a shank before folded showing recording sites and their

associated multiplexing transistors........................ ...................................... 121 6.3 The passive 3-D microelectrode with through-wafer via contact pads..........122 6.4 SEM images of the 3-D microelectrode with a pair of stopper layer............123 6.5 Schematic of an active 3-D microelectrode array......................................... 124

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ABSTRACT Wang, Ming-Fang, Ph.D., Purdue University, December 2007. A Three-Dimensional Si-Based Microelectrode for Neural Recording. Major Professor: Babak Ziaie.

Recording neural ensembles from awake, behaving animals has been an extremely successful experimental paradigm. In particular, recording neuronal ensembles allows real-time interpretation of neural codes as well as the detection of dynamic changes within a process. In recent years, microfabricated recording electrodes have attracted a great deal of attention for recording neural ensembles. These electrodes are fabricated using standard microelectronics and MEMS technologies and can offer a higher spatial resolution, better reproducibility, and superior recording capabilities. The most significant advantage of the silicon-based microelectrodes technology is that it enables the monolithic integration of electronics, such as amplifier, buffer, multiplexer and so on, as part of the probe structure. These active microelectrodes improve the quality of recording signals, reduce the output interconnections and provide the selection on recording sites, comparing with passive microelectrode (without integration with electronics). A three-dimensional (3-D) microfabricated electrode is particularly attractive since neurons are highly packed 3-D assemblies of cell bodies in the central nervous system; a 3-D microelectrode is advantageous in recording (or simulating) from a more realistic cytoarchitecture. Although one can fabricate an array of electrodes along a silicon shank, a truly 3-D configuration is harder to achieve. In this thesis, a microfabricated passive 3-D electrode in single unit format will be proposed and it overthrows the previous concept that 3-D configuration must comes from the array. The 3-D structure is accomplished in which the assembly of each shank is automated through a folding process, thus removing any manual handling, considerably simplifying the manufacturing. This 3-D electrode has several important advantages compared to the currently used wire electrodes and silicon-based microelectrodes. These include: 1) batch-scale fabrication, 2) easy achieve tetrode configuration for spike sorting, 3) superior signal-to-noise ratio without

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requiring the physical movement, 4) integration with active electronics, 5) 3-D configuration in a single unit format and can be extended to array and 6) scalability.

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1. INTRODUCTION

The central nervous system (CNS) composed of spinal cord and brain, which

divides into forebrain, midbrain, and hindbrain, represents the largest part of the nervous system in a human body. The other principal nervous system is peripheral nervous system (PNS) and it coordinates the body movements, receives external stimuli and responds to impending danger or stress. Unlike PNS, CNS is believed as a system dealt with information processing and has a fundamental role in the control of human behavior [1]. When the brain, the control center of CNS and a complex biological and electrochemical entity, is healthy it functions promptly and automatically. However, when the brain suffers problems, the results can be catastrophic. Some brain disorders are list below [2]:

1). neurogenetic diseases, e.g. Huntington’s disease, spinocerebellar ataxia, amyotrophic lateral sclerosis and muscular dystrophy.

2). genetic disorders: caused by a different form of a gene called a variation, or an alteration of a gene called a mutation, e.g. leukodystrophies, phenylketonuria, Tay-Sachs disease and Wilson disease.

3). degenerative diseases: the function of the affected tissues or organs will progressively deteriorate over time, e.g. diabetes, Parkinson’s disease and Alzheimer’s disease.

4). metabolic diseases: caused by genetic defects that result in missing or improperly constructed enzymes necessary for some step in the metabolic process of the cell, e.g. disorders of carbohydrate metabolism, disorders of amino acid metabolism and Gaucher’s disease.

5). cerebrovascular diseases: the arteries in the brain or connected to the brain are defective, e.g. stroke and vascular dementia.

6). trauma, e.g. spinal cord and head injury. 7). convulsive disorders, e.g. epilepsy.

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8). infectious diseases: a clinically evident disease resulting from the presence of pathogenic microbial agents, e.g. lower respiratory infection and AIDS dementia.

9). brain tumors. Improved comprehension of the CNS is a principal step in unraveling the puzzle

behind the complex human behavior and it also helps the design and implementation of advanced neural prostheses for a variety of disorders and the handicapped.

The ensemble activities of neurons are the information helped us clarify the relation between the physical features of the world and the brain’s interpretation of those features [3]. Measuring and analyzing the variant features, including the temporal relations among neuronal assemblies and assembly individuals from the invariant features represented by the physical world possible reveal clues about the perspective of the brain on its environment. However, one question is how one could proceed to test these competing frameworks. Generally, there are three well known approaches that scientists use to study on the brain. The first method is based on ‘temporally integrated field’ and it records the whole signals generated from the brain by placing electrodes on the scalp but without the ability to distinguish their origins. Furthermore, these dynamic and continuous time-variable signals can be analyzed by various mathematical software in the time and frequency domains, but these methods can only detect changes over large areas of the brain with few messages from sub-cortical activity. This method includes electroencephalography (EEG) and magnetoencephalography (MEG). The second method is established in ‘spatial mean field’ and it takes infrared pictures of the brain. This will measure the heat generated by the neurons activity and it contains functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and so on. Unfortunately, this approach fails to capture the essence of signal, temporal dynamics. About the third method, it records the action potential (spike) by implanted electrodes in the brain. The action potential is electrical pulse emitted by single neuron in the brain and is essential feature of animal life, rapidly carrying information within and between tissues. This independent and cell-level approach allows real-time interpretation of neural codes as well as the detection of dynamic changes within a process and has yielded significant progress in neuroscience.

Today, the recording of action potential is one of the most widely used techniques for studying CNS at the cellular level and the methodology of action potential detection by the conventional metal and glass microelectrodes have been used for a long time.

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Therefore, in order to offer higher spatial resolution, better reproducibility, superior recording capabilities and long-term recording, the techniques for fabricating the microelectrodes has changed considerably over the past twenty years by sharing the technology from solid state electronics. In addition, considering the fact that neurons are highly packed three-dimensional (3-D) assemblies of cell bodies in the CNS, a 3-D microelectrode is advantageous in recording or simulating from a more realistic cytoarchitecture. The 3-D microelectrodes are also superior in spike sorting and cell identification. In neuroscience, the spikes from a dedicated neuron are not recorded directly from the microelectrodes. This is because when the microelectrodes are implanted in the brain, the extracellular action potentials recorded on any microelectrode represent the simultaneous electrical activity of an unknown number of neurons. Based on these recorded signals and related mathematic algorithm, the action potentials will be identified, the number of neurons will be determined, and finally each spike will be assigned to the neuron that generated it. These three critical processes, so-called ‘spike sorting’, are the mandatory first step in all multiple spike train analyses [4].

1.1 A Short Introduction to Brain and Nerve Electrophysiology Anatomically, the brain can be separated into three regions, including the

forebrain, midbrain, and hindbrain. The forebrain contains the several lobes of the cerebral cortex that control higher functions, such as motor cortex involved in the planning, control, and execution of voluntary motor functions and auditory cortex responded for processing of auditory (sound) information, shown in Figure 1.1, while the midbrain and hindbrain are more involved with unconscious and autonomic functions. The brain is suspended in cerebrospinal fluid (CSF), which also fills spaces called ventricles inside it. Therefore, a brain that weighs 1500g in air weighs only 50g when suspended in CSF. The movement of CSF within brain is limited by the blood-brain barrier and the blood-cerebrospinal fluid barrier. Besides, the CSF can also protect brain and spinal cord from accidental shock. Although the brain is suspended in the fluid, it is easily damaged by compression. Maintaining the fluid surrounding the CNS at constant pressure can avoid damaging it.

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Figure 1.1 The human brain, lateral view. The lobes of the cerebral cortex include the frontal, temporal, occipital, and parietal lobes.

Neurons and glia are two broad groups of cells construct the brain and both of

them contain several different cell types which perform different functions. The neuron serves as the functional unit in the nervous system. Neurons convey information to other cells by generating action potentials and also receive messages from them; these constitute the fundamental operation among the brain cells. Humans have about 100 billion neurons in their brain alone. Unlike neurons in the role of functional unit, glial cells form a support system for neurons and in a roughly 10:1 proportion to neurons. Glial cells generate insulating myelin, give structure to the neuronal network, handle waste, and clean up neurotransmitters. Interconnected neurons form neural networks or neural ensembles. The neural networks are similar to normal artificial electrical circuits comprised device components (neurons) connected by metal wires (nerve fibers). However, they are not simple electrical circuits because typically neurons connect to thousand neurons at least. These extremely specialized neural networks build up nervous systems which are the basis of perception, different types of action, and higher cognitive function.

Although variable in size and shape, all neurons have three parts, including dendrites, cell body and axon, shown in Figure 1.2, and each of them has different functions. Dendrites receive information from another cell and then transmit the message to the cell body. The cell body is the central part of the neuron and contains

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nucleus, mitochondria and other organelles. The axon carries messages away from the cell body. The size and shape of the cell to be studied has a direct connection on the size of microelectrodes. Nerve cells normally range from 5 ~ 10 µm in diameter but it can be as large as 1000µm for some mammalian or in the giant squid.

Figure 1.2 Structure of a typical neuron [5].

Biological nerve cells are defined by a membrane about 75Å which surrounds the intracellular fluid and separates it from the extracellular fluid. The approximate compositions of both electrolytes are given in Figure 1.3. The primary extracellular ions are Na+ and Cl-, while intracellular ions come from K+ and HPO4

2-. These ions play an important role in generating transmembrane potential (usually ~ 100 mV with the inside of the cell). An action potential is a "spike" of electrical discharge that travels along the membrane of a cell. Action potentials are an essential feature of animal life, rapidly carrying information within and between tissues. They also occur in some plants. Action potentials can be created by many types of cells, but are used most extensively by the nervous system for communication between neurons and for transmitting information from neurons to other body tissues such as muscles and glands. Like all other cells, the plasma membrane of neurons has an unequal distribution of ions and electrical charges between the two sides of the membrane. The outside of the membrane has a positive charge, inside has a negative charge. This charge difference is a resting potential and is measured in millivolts. Passage of ions across the cell membrane passes the electrical charge along the cell. The voltage potential is -65mV of a cell at rest (resting potential). Resting potential results from differences between sodium and potassium positively charged ions and negatively charged ions in the

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