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11/21/14 27 November 2014 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. GBM8320 - Dispositifs Médicaux Intelligents 2 1 11/21/14 • Many types of cells in the body have the ability to undergo a transient electrical depolarization and repolarization • These are either triggered by external depolarization (in the heart) or by intracellular, spontaneous mechanisms • Cells that exhibit the ability to generate electrical signals are called electrogenic cells • The most prominent electrogenic cells include brain cells or neurons and heart cells or cardiomyocytes. (e.g. cardiac pacemaker cells). GBM8320 - Dispositifs Médicaux Intelligents 3 • Electrogenic cells such as neurons contain ion channels, selectively enable the permeation of certain ions such as sodium or potassium • In a transient change of conductivity, the overall ion flux generates an action potential, which is the elementary electrical signal in biological systems. Jenkner et al, “Cell-based CMOS sensor …,” IEEE ISSC, V. 39, 2004. GBM8320 - Dispositifs Médicaux Intelligents 4 2 11/21/14 • Electrical activity is explained by differences in ion concentrations within the body (sodium, Na+; cloride, Cl–; potassium, K+) • A potential difference occurs between 2 points with different ionic concentrations • Cell membranes at rest are more permeable to some ions (e.g. K+, Cl–) than others (e.g. Na+) – Na+ ions are pumped out of the cells, while K+ ions are pumped in – Due to a difference in rates of pumping, a difference in positive ion concentration results – A negative potential (–70 mV ) is established between the inside and outside of the cell. GBM8320 - Dispositifs Médicaux Intelligents 5 • When a cell is electrically stimulated, the permeability of the cell membrane changes – Na+ ions rush into the cell, and K+ ions rush out – Again, due to a difference in rates of flow, the ion concentration changes (more positive ions inside cell than outside) – Cellular potential becomes positive (40 mV) – Cell is said to be depolarized. • After the stimulus, the permeability of the cell membrane returns to its original value, and the rest potential is restored – Due to unequal pumping rates of ions – Time taken for restoration is called the refractory period – Cell is said to be repolarized during this time • The resulting variation in cellular potential with time is known as the action potential. GBM8320 - Dispositifs Médicaux Intelligents 6 3 11/21/14 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. GBM8320 - Dispositifs Médicaux Intelligents 7 • Biopotential electrodes convert ionic conduction to electronic conduction so that biopotential signals can be viewed and/or stored • Different electrodes types include surface macroelectrodes, indwelling macroelectrodes & microelectrodes (cuff or other shapes) • Skin and other body tissues act as electrolytic solutions ! GBM8320 - Dispositifs Médicaux Intelligents 8 4 11/21/14 • Charge carriers in electrode materials: – Metals (e.g. Pt) : electrons – Semiconductors (e.g. n-Si) : electrons and holes – Solid electrolytes (e.g. lanthanum fluoride - LaF3) : ions – Insulators (e.g. SiO2): no charge carriers – Mixed conductors (e.g. IrOx) : ions and electrons – Solution (e.g. 1 M NaCl in H2O): solvated ions. Inner Helmholtz plane (IHP) Outer Helmholtz plane (OHP) Gouy-Chapman layer (GCL) Double layer Webster, J.G., Medical Instrumentation, Wiley, 4Ed, 2009, GBM8320 - Dispositifs Médicaux Intelligents 9 • Electrode discharges some metallic ions into electrolytic solution – Increase in # free electrons in electrode – Increase in # positive cations (electric charge) in solution; OR • Ions in solution combine with metallic electrodes – Decrease in # free electrons in electrode – Decrease in # positive cations in solution. • As a result, a charge gradient builds up between the electrode and electrolyte and this in turn creates a potential difference. GBM8320 - Dispositifs Médicaux Intelligents 10 5 11/21/14 General Ionic Equations a) C ↔ C n + + ne − b) Am − ↔ A + me − where n and m are les valences • If the electrode is of the same material as the cations, then this material gets oxidized and enters the electrolyte as a cation and electrons remain at the electrode & flow in the external circuit; • If anion can be oxidized at the electrode to form a neutral atom, one or two electrons are given to the electrode. • The dominating reaction can be inferred from the following : - Current flow from electrode to electrolyte : Oxidation (Loss of e-) - Current flow from electrolyte to electrode : Reduction (Gain of e-). GBM8320 - Dispositifs Médicaux Intelligents 11 • For both mechanisms, (Oxidation = Loss of e-, and Reduction = Gain of e-), two parallel layers of oppositely charged ions are produced; i.e. the electrode double layer : - e.g. when metal ions recombine with the electrode. • The excess of negative anions is replaced with positive cations in the case of metal ions discharging into solution, and Vh is then < 0. GBM8320 - Dispositifs Médicaux Intelligents 12 6 11/21/14 Geddes, Principles of Applied Biomedical Instrumentation, Wiley, 1989 GBM8320 - Dispositifs Médicaux Intelligents 13 • A characteristic potential difference established by the electrode and its surrounding electrolyte which depends on the metal, concentration of ions in solution and temperature. • Reason for half-cell potential : Charge separation at interface : Oxidation or reduction reactions at the electrode-electrolyte interface lead to a double-charge layer, similar to that which exists along electrically active biological cell membranes. • Half-cell potential cannot be measured without a second electrode. The half-cell potential of the standard hydrogen electrode has been arbitrarily set to zero. Other half cell potentials are expressed as a potential difference with this electrode. GBM8320 - Dispositifs Médicaux Intelligents 14 7 11/21/14 • Convention: The hydrogen electrode is defined as having a half-cell potential of zero. • The half-cell potentials of all other electrode materials is measured with respect to this hydrogen electrode. • Eo : Standard half-cell potential. * * Standard Hydrogen electrode GBM8320 - Dispositifs Médicaux Intelligents 15 GBM8320 - Dispositifs Médicaux Intelligents 16 • Electrode material is metal + salt or polymer selective membrane. 8 11/21/14 • If there is a current between the electrode and electrolyte, the observed half-cell potential is often altered due to polarization, then an overpotential occurs: Overpotential Difference between observed and zero-current half-cell potentials Resistance Current changes resistance of electrolyte and thus, a voltage drop results. Activation The activation energy barrier depends on the direction of current and determines kinetics Concentration Changes in distribution of ions at the electrodeelectrolyte interface VP= VR+ VC+ VA + E0 Note: Polarization and impedance of the electrode are two of the most important electrode properties to consider. Eo : Standard half-cell potential GBM8320 - Dispositifs Médicaux Intelligents 17 • When two aqueous ionic solutions of different concentration are separated by an ion-selective semi-permeable membrane, an electric potential exists across this membrane. • For the general oxidation-reduction reaction a A + b B ↔ gC + dD + ne − • The Nernst equation for half-cell potential is E = E0 + RT ⎡ aCγ aDδ ⎤ ln nF ⎢⎣ aαA a βB ⎥⎦ where Eo and E are Standard & half-cell potentials, a : Ionic activity (generally same as concentration), and n : Number of valence electrons involved. Note: for a metal electrode, 2 processes can occur at the electrolyte interfaces: – A capacitive process resulting from the redistribution of charged and polar particles with no charge-transfer between the solution and the electrode – A component resulting from the electron exchange between the electrode and a redox species in the solution termed faradaic process. GBM8320 - Dispositifs Médicaux Intelligents 18 9 11/21/14 • Perfectly Polarizable Electrodes Used for stimulation These are electrodes in which no actual charge crosses the electrodeelectrolyte interface when a current is applied. The current across the interface is a displacement current and the electrode behaves like a capacitor. Example : Platinum Electrode (Noble metal) • Perfectly Non-Polarizable Electrode Used for recording These are electrodes where current passes freely across the electrodeelectrolyte interface, requiring no energy to make the transition. These electrodes see no overpotentials. Example : Ag/AgCl electrode GBM8320 - Dispositifs Médicaux Intelligents 19 Relevant ionic equations Ag ↔ Ag + + e − Ag + + Cl − ↔ AgCl ↓ Cl2 AgCl- Governing Nernst Equation E = E 0Ag + RT ⎡ K s ⎤ ln ⎢ ⎥ nF ⎣⎢ aCl − ⎦⎥ Solubility product of AgCl Fabrication of Ag/AgCl electrodes 1. Electrolytic deposition of AgCl 2. Sintering process forming pellet electrodes GBM8320 - Dispositifs Médicaux Intelligents 20 10 11/21/14 What • If a pair of electrodes is in an electrolyte and one moves with respect to the other, a potential difference appears across the electrodes known as the motion artifact. This is a source of noise and interference in bio-potential measurements. Why • When the electrode moves with respect to the electrolyte, the distribution of the double layer of charge on polarizable electrode interface changes. This changes the half-cell potential temporarily. Note • Motion artifact is minimal for non-polarizable electrodes (Measurement electrodes – AgCl). GBM8320 - Dispositifs Médicaux Intelligents 21 Rd+Rs Corner frequency Rs Frequency Response • • • • Cd : Capacitance of electrode-electrolyte interface Rd : Resistance of electrode-electrolyte interface Rs : Resistance of electrode lead wire Ecell : Half-cell potential for electrode. GBM8320 - Dispositifs Médicaux Intelligents 22 11 11/21/14 • Recording/Stimulating Sites: Thin-film materials such as gold, platinum, and iridium. Recording Interface Interconnect Resistance Biopotential Shunt Capacitances Recording Amplifier GBM8320 - Dispositifs Médicaux Intelligents • Extracellular action potentials have amplitude in the range of 50-500µV = Very low-level input signals • Total system input-referred noise should be < 20µVrms. • Biological frequency band: 100Hz-10kHz • System noise= Electrode noise + Preamplifier noise • Main source of electrode noise is thermal noise: 23 Vne2 = 4kTRN Δf - RN is noise resistance (real part of probe impedance magnitude). - Δf is recording bandwidth. GBM8320 - Dispositifs Médicaux Intelligents 24 12 11/21/14 • A body-surface electrode is placed against skin, showing the total electrical equivalent circuit obtained in this situation. • Each circuit element on the right is at approximately the same level at which the physical process that it represents would be in the lefthand diagram. Webster, Medical instrumentation: application and design. 3Ed, Wiley 1998. GBM8320 - Dispositifs Médicaux Intelligents 25 GBM8320 - Dispositifs Médicaux Intelligents 26 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. 13 11/21/14 Metal-plate electrodes Large surface: Ancient, therefore still used, ECG • Metal disk with stainless steel; platinum or gold coated • • • • EMG, EEG Smaller diameters Motion artifacts Disposable foam-pad: Cheap! (a) Metal-plate electrode used for application to limbs. (b) Metal-disk electrode applied with surgical tape. (c) Disposable foam-pad electrodes, often used with ECG GBM8320 - Dispositifs Médicaux Intelligents Insulating package 27 Metal disk Double-sided Adhesive-tape ring (b) (a) Snap coated with Ag-AgCl (a) Recessed electrode with hot structure; (b) Cross-sectional view of electrode (a) (c) Cross-sectional view of another disposable electrode. Plastic cup Foam pad Electrolyte gel in recess External snap Gel-coated sponge Plastic disk Reusable Disposable Dead cellular material Tack Capillary loops Germinating layer (c) GBM8320 - Dispositifs Médicaux Intelligents 28 14 11/21/14 • Body contours are often irregular • Regularly shaped rigid electrodes may not always work • Special case : infants • Used materials - Polymer or nylon with silver - Carbon filled silicon rubber (Mylar film). (a) Carbon-filled silicone rubber electrode. (b) Flexible thin-film neonatal electrode. (c) Cross-sectional view of the thin-film electrode in (b) • Needle and wire electrodes for percutaneous measurement of biopotentials: • Insulated needle electrode • Coaxial needle electrode. • Bipolar coaxial electrode. • Fine-wire electrode connected to hypodermic needle, before being inserted. • Cross-sectional view of skin and muscle, showing coiled fine-wire electrode in place. GBM8320 - Dispositifs Médicaux Intelligents 29 GBM8320 - Dispositifs Médicaux Intelligents 30 15 11/21/14 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. GBM8320 - Dispositifs Médicaux Intelligents • Electrodes for detecting fetal ECG (Use of intracutaneous needles) • Suction electrode • Helical electrode • Electrodes for Cardiac stimulation. 31 • Electrodes for detecting biopotentials • Wire-loop electrode • Platinum-sphere cortical surface potential electrode • Multielement depth electrode. GBM8320 - Dispositifs Médicaux Intelligents 32 16 11/21/14 • ENG measurement (three contacts) • Stimulation (2 contacts) • Cuff electrodes • Helical electrodes • Pins electrodes • Multicontacts electrodes • etc GBM8320 - Dispositifs Médicaux Intelligents 33 GBM8320 - Dispositifs Médicaux Intelligents 34 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. 17 11/21/14 Insulated leads Contacts Ag/AgCl electrodes Ag/AgCl electrodes Contacts Insulated leads Base Base Exposed tip Tines (a) (b) Examples of microfabricated electrode arrays: (a) One-dimensional plunge electrode array (b) Two-dimensional array, and (c) Three-dimensional array. • Base (c) GBM8320 - Dispositifs Médicaux Intelligents • Beam-lead multiple electrodes : Wise, et al. • Multielectrode silicon probe : Drake et al. • Multiple-chamber electrode : Prohaska et al. • Peripheral-nerve electrode : Edell. SiO2 insulated Au probes 35 Bonding pads Insulated lead vias Exposed electrodes Silicon probe Si substrate Exposed tips (b) (a) Miniature insulating chamber Channels Hole Silicon chip Lead via Silicon probe Electrode (c) Contact metal film (d) GBM8320 - Dispositifs Médicaux Intelligents 36 18 11/21/14 An 8-probe array of 64 contacts each GBM8320 - Dispositifs Médicaux Intelligents 37 • Wire-EDM cut • Surface electropolish • Oxalic acid attack • Platinum deposition • Epoxy base • Support Grinding • Assembly. Robofil 2030 GBM8320 - Dispositifs Médicaux Intelligents 38 19 11/21/14 • Surface electropolish • Oxalic acid attack • Platinum deposition • Epoxy base • Support Grinding • Assembly. GBM8320 - Dispositifs Médicaux Intelligents 39 GBM8320 - Dispositifs Médicaux Intelligents 40 • Introduction − Electrogenic cell • Electrode/electrolyte interface − − − − Electrical double layer Half-cell potential Polarization Electrode equivalent circuits • Biopotential electrodes − − − − − − Body surface electrodes Internal electrodes Implantable electrodes Electrode arrays Microfabricated electrodes Microelectrodes. 20 11/21/14 Structure of a metal microelectrode for intracellular recordings. Structures of two supported metal microelectrodes: (a) Metal-filled glass micropipet (b) Glass micropipet or probe, coated with metal film. GBM8320 - Dispositifs Médicaux Intelligents 41 • The electrical activity of cells can be recorded without disrupting the cell membrane using extracellular recording techniques • For extracellular recordings, the cells are located directly on top of a transducing element, which is, in most cases, either a metallic electrode or an open-gate transistor • When electrical activity or a so-called action potential in a cell occurs, ions flow across the cell membrane within msec. • Ions sensitive transistors can be used to transduce the cells activity. GBM8320 - Dispositifs Médicaux Intelligents 42 21 11/21/14 • When a cell is close to a transducer, the moving ions generate an electric field or voltage, which can be recorded by the metallic microelectrode or field-effect transistor • Extracellular recordings are non-invasive (no puncturing of the cell membrane) • Models: - Metal electrode - Open fieldeffect transistor. GBM8320 - Dispositifs Médicaux Intelligents 43 • Two main advantages in using integrated-circuit (IC) or CMOS technology: – Connectivity: larger numbers of transducers or electrodes can be addressed by on-chip multiplexing architectures – Signal quality; the signal is conditioned right at the electrode by means of dedicated circuitry units (filters, amplifiers) • The use of CMOS technology allows to realize a large number of electrodes on a small system chip • On-chip microelectronics, as provided by the use of IC or CMOS technology, translate into system capability: signal conditioning can be performed on-chip, ensuring that weak neural signals are faithfully recorded; GBM8320 - Dispositifs Médicaux Intelligents 44 22 11/21/14 • A CMOS system also enables a bidirectional communication via the electrodes (stimulation and recording); • Smart switching schemes allow for stimulating the cell ensemble via an arbitrarily selectable set of electrodes, all while recording from other electrodes uninterruptedly during stimulation • On-chip analog-to-digital conversion means that such chip produces a robust signal that may be easily manipulated and transferred without compromising its information content • Moreover, the use of on-chip electronics allows for the monolithic integration of the complete system on a single chip, which leads to small system dimensions and low power consumption, a key requirement for implantable devices GBM8320 - Dispositifs Médicaux Intelligents 45 • The use of multiplexers enables the integration of a large number of electrodes or transducers so that measurements at high spatiotemporal resolution become feasible • Traditional Microelectrode arrays (MEAs) without multiplexers usually offer 64 electrodes with each electrode needing a connection to external circuitry, which adds parasitic capacitance and attenuates the weak signals • CMOS-based MEAs comprise up to 16,384 electrodes and the needed addressing circuitry on the same chip • A disadvantage of CMOS ICs is that silicon is not transparent to visible light in contrast to standard cell culture substrates used in biology GBM8320 - Dispositifs Médicaux Intelligents 46 23 11/21/14 • The IC or its components can corrode upon operation and long-term exposure to liquids (salt water) • A good packaging solution is needed: – To protect the IC against metabolism products – To prevent the cells from being poisoned or disturbed by toxic materials released by the IC, such as the CMOS metal aluminum that dissolves in saline solution. Notes : • Make a better electrode • Research different electrode technologies – Ion selective, immunosensors, ISFET, electrochemical – MEMS microelectrode technologies – Polymer based electrodes.. GBM8320 - Dispositifs Médicaux Intelligents 47 24