11/21/14. Introduction Electrogenic cell

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1 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. GBM Dispositifs Médicaux Intelligents 2 1

2 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). GBM 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, GBM Dispositifs Médicaux Intelligents 4 2

3 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. GBM 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. GBM Dispositifs Médicaux Intelligents 6 3

4 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. GBM 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! GBM Dispositifs Médicaux Intelligents 8 4

5 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) Webster, J.G., Medical Instrumentation, Wiley, 4Ed, 2009, Double layer GBM 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. GBM Dispositifs Médicaux Intelligents 10 5

6 General Ionic Equations C C a) b) A m n+ + ne 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-). GBM 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. GBM Dispositifs Médicaux Intelligents 12 6

7 Geddes, Principles of Applied Biomedical Instrumentation, Wiley, 1989 GBM 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. GBM Dispositifs Médicaux Intelligents 14 7

8 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 GBM Dispositifs Médicaux Intelligents 15 Electrode material is metal + salt or polymer selective membrane. GBM Dispositifs Médicaux Intelligents 16 8

9 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. Concentration Changes in distribution of ions at the electrodeelectrolyte interface Activation The activation energy barrier depends on the direction of current and determines kinetics V = V + V + V + E P R C A 0 Note: Polarization and impedance of the electrode are two of the most important electrode properties to consider. Eo : Standard half-cell potential GBM 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 The Nernst equation for half-cell potential is aa + bb gc + dd + ne E RT a a + ln nf a γ δ 0 C D = E α β AaB 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. GBM Dispositifs Médicaux Intelligents 18 9

10 Perfectly Polarizable Electrodes 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) Used for stimulation 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 GBM Dispositifs Médicaux Intelligents 19 Relevant ionic equations Ag Ag Ag + + Cl + + e AgCl AgCl- Fabrication of Ag/AgCl electrodes 1. Electrolytic deposition of AgCl Cl2 Governing Nernst Equation E = E 2. Sintering process forming pellet electrodes 0 Ag + RT nf K ln a Cl s Solubility product of AgCl GBM Dispositifs Médicaux Intelligents 20 10

11 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). GBM Dispositifs Médicaux Intelligents 21 Rd+Rs Corner frequency Rs Cd : Capacitance of electrode-electrolyte interface Rd : Resistance of electrode-electrolyte interface Rs : Resistance of electrode lead wire Ecell : Half-cell potential for electrode. Frequency Response GBM Dispositifs Médicaux Intelligents 22 11

12 Recording/Stimulating Sites: Thin-film materials such as gold, platinum, and iridium. Recording Interface Interconnect Resistance Shunt Capacitances Biopotential Recording Amplifier GBM Dispositifs Médicaux Intelligents 23 Extracellular action potentials have amplitude in the range of µV = Very low-level input signals Total system input-referred noise should be < 20µV rms. Biological frequency band: 100Hz-10kHz System noise= Electrode noise + Preamplifier noise Main source of electrode noise is thermal noise: V 2 ne = 4kTR Δf - R N is noise resistance (real part of probe impedance magnitude). - Δf is recording bandwidth. N GBM Dispositifs Médicaux Intelligents 24 12

13 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 GBM Dispositifs Médicaux Intelligents 25 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. GBM Dispositifs Médicaux Intelligents 26 13

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 GBM Dispositifs Médicaux Intelligents 27 Insulating package Metal disk Double-sided Adhesive-tape ring ( b ) ( a ) Electrolyte gel in recess Reusable (a) Recessed electrode with hot structure; (b) Cross-sectional view of electrode (a) (c) Cross-sectional view of another disposable electrode. Snap coated with Ag-AgCl Plastic cup Foam pad Tack Capillary loops External snap Gel-coated sponge Plastic disk ( c ) Dead cellular material Germinating layer Disposable GBM Dispositifs Médicaux Intelligents 28 14

15 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.( film (Mylar (a) Carbon-filled silicone rubber electrode. (b) Flexible thin-film neonatal electrode. (c) Cross-sectional view of the thin-film electrode in (b) GBM Dispositifs Médicaux Intelligents 29 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. GBM Dispositifs Médicaux Intelligents 30 15

16 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. GBM Dispositifs Médicaux Intelligents 31 Electrodes for detecting fetal ECG (Use of intracutaneous needles) Suction electrode Helical electrode Electrodes for Cardiac stimulation. Electrodes for detecting biopotentials Wire-loop electrode Platinum-sphere cortical surface potential electrode Multielement depth electrode. GBM Dispositifs Médicaux Intelligents 32 16

17 ENG measurement (three contacts) Stimulation (2 contacts) Cuff electrodes Helical electrodes Pins electrodes Multicontacts electrodes etc GBM Dispositifs Médicaux Intelligents 33 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. GBM Dispositifs Médicaux Intelligents 34 17

18 Contacts Insulated leads Ag/AgCl electrodes Contacts Ag/AgCl electrodes Insulated leads ( b ) ( a ) Base Base Exposed tip Tines Examples of microfabricated electrode arrays: (a) One-dimensional plunge electrode array (b) Two-dimensional array, and (c) Three-dimensional array. ( c ) Base GBM Dispositifs Médicaux Intelligents 35 Beam-lead multiple electrodes : Wise, et al. SiO2 insulated Au probes Insulated lead vias Exposed electrodes Bonding pads Multielectrode silicon probe : Drake et al. Si substrate ( b ) ( a ) Exposed tips Silicon probe Multiple-chamber electrode : Prohaska et al. Miniature insulating chamber Hole Lead via Channels Silicon chip Peripheral-nerve electrode : Edell. Electrode Silicon probe ( d ) ( c ) Contact metal film GBM Dispositifs Médicaux Intelligents 36 18

19 11/21/14 An 8-probe array of 64 contacts each GBM Dispositifs Médicaux Intelligents 37 Wire-EDM cut Surface electropolish Oxalic acid attack Platinum deposition Epoxy base Support Grinding Assembly. Robofil 2030 GBM Dispositifs Médicaux Intelligents 38 19

20 Surface electropolish Oxalic acid attack Platinum deposition Epoxy base Support Grinding Assembly. GBM Dispositifs Médicaux Intelligents 39 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. GBM Dispositifs Médicaux Intelligents 40 20

21 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. GBM 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. GBM Dispositifs Médicaux Intelligents 42 21

22 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. GBM 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; GBM Dispositifs Médicaux Intelligents 44 22

23 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 GBM 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 GBM Dispositifs Médicaux Intelligents 46 23

24 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.. GBM Dispositifs Médicaux Intelligents 47 24