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2 Table of Contents 1. Basic Concepts of Medical Instrumentation2. Basic Sensors and Principles 3. Amplifiers and Signal Processing 4. The Origin of Biopotentials 5. Biopotential Electrodes

3 Basic Concepts of Medical InstrumentationChapter 1-Webster Basic Concepts of Medical Instrumentation

4 Generalized instrumentation systemPerceptible output Output display Control And feedback Signal processing Data transmission storage Variable Conversion element Sensor Primary Sensing Measurand Calibration signal Radiation, electric current, or other applied energy Power source Figure 1.1 The sensor converts energy or information from the measurand to another form (usually electric). This signal is the processed and displayed so that humans can perceive the information. Elements and connections shown by dashed lines are optional for some applications.

5 Measurand: Physical quantityBiopotential Pressure Flow Dimensions (imaging) Displacement (velocity, acceleration, force) Impedance Temperature Chemical Concentration

6 Sensor and Transducer Transducer SensorConverts one form of energy to another Sensor Converts a physical measurand to an electrical output Interface with living system Minimize the energy extracted Minimally invasive displacement electric voltage pressure diaphragm Strain gage

7 Signal Conditioning Amplification Filtering Impedance matchingAnalog/Digital for signal processing Signal form (time and frequency domains)

8 Output Display Numerical Graphical Discrete or continuous VisualHearing

9 Auxiliary Element Calibration SignalControl and Feedback (auto or manual) Adjust sensor and signal conditioning

10 1.3 Alternative Operational ModesDirect Mode: Measurand is readily accessible Temperature Heart Beat Indirect Mode: desired measurand is measured by measuring accessible measurand. Morphology of internal organ: X-ray shadows Volume of blood pumped per minute by the heart: respiration and blood gas concentration Pulmonary volumes: variation in thoracic impedance

11 1.3 Sampling and Continuous ModesSampling and collecting data will depend on the following: The rate of change in the measurand Condition of the patient Generating and Modulating Sensors Generating sensors produce their outputs from energy taken from measurand (Photovoltaic cell) Modulating Sensors uses the measurand to alter the flow of energy from an external source (Photoconductive cell) Analog and Digital Modes Real-Time and Delayed-Time Modes

12 1.4 Medical Measurement ConstraintsMagnitude and frequency range of medical measurand are very low Proper measurand-sensor interface cannot be obtained Medical variables are seldom deterministic External energy must be minimized to avoid any damage Equipment must be reliable

13 1.5 Classification of Medical InstrumentQuantity that is sensed pressure, flow, temp Principle of transduction resistive, capacitive, electrochemical, ultrasound Organ system cardiovascular, pulmonary, nervous Medicine specialties pediatrics, cardiology, radiology

14 1.6 Interfering and Modifying InputsDesired Inputs: measurands that the instrument is designed to isolate. Interfering Inputs: quantities that unintentionally affect the instrument as a consequence of the principles used to acquire and process the desired inputs. Modifying Inputs: undesired quantities that indirectly affect the output by altering the performance of the instrument itself.

15 1.6 Interfering and Modifying InputsElectrodes 60-Hz ac magnetic field Displacement currents Differential amplifier +  Vcc Vcc Z1 Zbody Z2 vo vecg Desired input: Electrocardiographic voltage Vecg Interfering input: voltage due to 60-Hz Figure 1.2 Simplified electrocardiographic recording system Two possible interfering inputs are stray magnetic fields and capacitively coupled noise. Orientation of patient cables and changes in electrode-skin impedance are two possible modifying inputs. Z1 and Z2 represent the electrode-skin interface impedances.

16 1.7 Compensation TechniquesTo eliminate interfering and modifying input: Alter the design of essential instrument components to be less sensitive to interference. (preferred) Adding new components designed to offset the undesired inputs.

17 1.7 Compensation TechniquesInherent Insensitive Negative Feedback to minimize Gd which is effected by the modifying inputs (xd – Hfy)Gd = y (1.1) xdGd = y(1 + HfGd) (1.2) (1.3) Signal Filtering (electric, mechanical, magnetic) Opposing Inputs

18 Compensation Techniques- ExampleAn amplifier with gain 10 that has 20% fluctuation due to temperature and environmental change. How will compensate the system to minimize the fluctuation?

19 1.8 Biostatistics Applications of Statistics to medical dataDesign experiment Clinical Study: summarize, explore, analyze Draw inference from data: estimation, hypothesis Evaluate diagnostic procedures: assist clinical decision making

20 Medical Research Studies- Observational: Characteristics of patients are observed and recorded Case-series: describe characteristic of group Case-control: observe group that have some disease Cross-sectional: Analyze characteristics of patients Cohort: determine if a particular characteristic is a precursor for a disease. Experimental Intervention: Effect of a medical procedure or treatment is investigated Controlled: Comparing outcomes to drug and placebo Uncontrolled: No placebo and no comparison Concurrent controls: patient are selected the same way and for the same time. Double-blind

21 Statistical MeasurementsMeasures of the mean and central tendency Mean Median: Middle value (used for skewed data) Mode: is the observation that occurs most frequently Geometric Mean: used with data on a logarithmic scale

22 Statistical MeasurementsMeasure of spread or dispersion of data Range: Difference between the largest and smallest observation Standard deviation: is a measure of the spread of data about the mean For symmetric distribution 75% of the data lies between (mean - 2s) and (mean + 2s) Coefficient of variation: standardize the variation to compare data measured in different scales.

23 Statistical MeasurementsPercentile: gives the percentage of a distribution that is less than or equal to the percentile number. Standard error of the mean (SEM): Express the variability to be expected among the mean in future samples. Correlation Coefficient r: is a measure of a linear relationship between numerical variables x and y for paired observations

24 Estimation and confidence of interval:Methods for inference about a value in a population of subjects from a set of observations. Estimation and confidence of interval: are used to estimate specific parameters such as the mean and the variance. Hypothesis testing and P-value: reveals whether the sample gives enough evidence for us to reject the null hypothesis. P-value indicates how often the observed difference would occur by chance alone.

25 Methods for measuring the accuracy of a diagnostic procedureSensitivity of a test: Probability of its yielding positive results in patients who actually have the disease. Specificity of a test: Probability of its yielding negative results in patients who do not have the disease Prior Probability: the prevalence of the condition prior to the test.

26 Characteristics of Instrument PerformanceTwo classes of characteristics are used to evaluated and compare new instrument Static Characteristics: describe the performance for dc or very low frequency input. Dynamic Characteristics: describe the performance for ac and high frequency input.

27 1.9 Generalized Static CharacteristicsParameters used to evaluate medical instrument: Accuracy: The difference between the true value and the measured value divided by the true value Precision: The number of distinguishable alternatives from which a given results is selected {2.434 or 2.43} Resolution: The smallest increment quantity that can be measured with certainty Reproducibility: The ability to give the same output for equal inputs applied over some period of time.

28 1.9 Generalized Static CharacteristicsParameters used to evaluate medical instrument: Statistical Control: Systematic errors or bias are tolerable or can be removed by calibration. Statistical Sensitivity: the ratio of the incremental output quantity to the incremental input quantity, Gd.

29 Finding static sensitivity Gd using line equation with the minimal sum of the squared difference between data points and the line

30 Zero Drift: all output values increase or decrease by the same amount due to manufacturing misalignment, variation in ambient temperature, vibration,…. Sensitivity Drift: Output change in proportion to the magnitude of the input. Change in the slope of the calibration curve. Figure 1.3 (b) Static sensitivity: zero drift and sensitivity drift. Dotted lines indicate that zero drift and sensitivity drift can be negative.

31 Independent nonlinearity- A% deviation of the reading - B% deviation of the full scale x1 y1 (x1 + x2) Linear Linear (y1 + y2) system system and and x2 y2 Kx1 Ky1 Linear Linear system system (a) Least-squares straight line y (Output) B% of full scale A% of reading Figure 1.4 (a) Basic definition of linearity for a system or element. The same linear system or element is shown four times for different inputs. (b) A graphical illustration of independent nonlinearity equals A% of the reading, or B% of full scale, whichever is greater (that is, whichever permits the larger error). Overall tolerance band xd (Input) Point at which Input Ranges (I): Minimum resolvable input < I < normal linear operating range A% of reading = B% of full scale (b)

32 Example A linear system described by the following equation y=2x+3. Find the overall tolerance band for the system if the input range is 0 to 10 and its independent nonlinearity is 0.5% deviation of the full scale and 1.5% deviation of the reading.

33 Input Impedance: disturb the quantity being measured.Xd1 : desired input (voltage, force, pressure) Xd2 : implicit input (current, velocity, flow) P = Xd1.Xd2 :Power transferred across the tissue-sensor interface Generalized input impedance Zx Goal: Minimize P, when measuring effort variable Xd1, by maximizing Zx which in return will minimize the flow variable Xd2. Loading effect is minimized when source impedance Zs is much smaller then the Zx

34 1.10 Generalized Dynamic CharacteristicsMost medical instrument process signals that are functions of time. The input x(t) is related to the output y(t) by ai and bi depend on the physical and electrical parameters of the system. Transfer Functions The output can be predicted for any input (transient, periodic, or random)

35 Frequency Transfer FunctionCan be found by replacing D by j Example: If x(t) = Ax sin ( t) then y(t) = |H()| Ax sin ( t + /_H())

36 Zero-Order Instrument a0 y(t) = b0 x(t)K: static sensitivity Figure 1.5 (a) A linear potentiometer, an example of a zero-order system. (b) Linear static characteristic for this system. (c) Step response is proportional to input. (d) Sinusoidal frequency response is constant with zero phase shift.

37 First-Order InstrumentWhere  is the time constant

38 First-Order InstrumentOutput y(t) R + + Slope = K = 1 x(t) C y(t)   Input x(t) (a) (b) x(t) Log Y (j scale X (j 1 1.0 0.707 S L L S Log scale  t (c) (d)  y(t) 1 0° S Log scale  L 0.63  45° 90° S L t Example 1.1: High-pass filter

39 Second-Order InstrumentMany medical instrument are 2nd order or higher Operational Transfer Function Frequency Transfer Function

40 2nd order mechanical force-measuring InstrumentOutput y ( t ) (b) (d) (c) 1 Ks x(t) y(t) yn yn + 1 Resonance 2 Log scale -90° 0.5 -180° Log scale  K Input x(t) Slope K = 0° n Y (j X (j  displacement (a) Input Force x(t) B = viscosity constant Ks = spring constant Natural freq. Damping ratio Figure 1.7 (a) Force-measuring spring scale, an example of a second-order instrument. (b) Static sensitivity. (c) Step response for overdamped case  = 2, critically damped case  = 1, underdamped case  = (d) Sinusoidal steady-state frequency response,  = 2,  = 1,  = 0.5.

41 Overdamped Critically damped Underdamped Damped natural freq. y(t) 1Ks 0.5 Damped natural freq. t

42 Example 1.2: for underdamped second-order instruments, find the damping ratio from the step responseand Logarithmic decrement

43 Time Delay System Y (j X (j Log scale K Log scale   Log scale 0°

44 Design Criteria Figure 1.8 Design process for medical instruments Choice and design of instruments are affected by signal factors, and also by environmental, medical, and economic factors.

45 Commercial Medical Instrumentation Development ProcessIdeas: come from people working in the health care Detailed evaluation and signed disclosure Feasibility analysis and product description Medical need Technical feasibility Brief business plan (financial, sales, patents, standards, competition) Product Specification (interface, size, weight, color) “What” is required but nothing about “how” Design and development (software and hardware)

46 Commercial Medical Instrumentation Development ProcessPrototype development Testing on animals or human subjects Final design review (test results for, specifications, subject feedback, cost) Production (packaging, manual and documents) Technical support

47 Regulation of Medical DevicesMedical devices is “any item promoted for a medical purpose that does not rely on chemical action to achieve its intended effect” 2 Ways for Medical Devices Classification First Way: (based on potential hazards) Class I: general controls Class II: performance standards Class III: premarketing approval Second Method: (see Table 1.2 in textbook) preamendment, postamendment, substantially equivalent, implant, custom, investigational, transitional

48 Regulation of Medical DevicesSecond Way of classifications: (see Table 1.2 in textbook) Preamendment: Devices on the market before 5/28/1976 Postamendment: Devices on the market after 5/28/1976 Substantially equivalent: Equivalent to preamendment devices Implant: devices inserted in human body and intended to remain there for >30 days. Custom: Devices not available to other licensed and not in finished form Investigational: Unapproved devices undergoing clinical investigation Transitional: devices that were regulated as drugs and now defined as medical devices

49 Basic Sensors and PrinciplesChapter 2-Webster Basic Sensors and Principles

50 Transducer, Sensor, and ActuatorTransducer: a device that converts energy from one form to another Sensor: converts a physical parameter to an electrical output (a type of transducer, e.g. a microphone) Actuator: converts an electrical signal to a physical output (opposite of a sensor, e.g. a speaker) Type of Sensors Displacement Sensors: resistance, inductance, capacitance, piezoelectric Temperature Sensors: Thermistors, thermocouples Electromagnetic radiation Sensors: Thermal and photon detectors

51 Displacement MeasurementsUsed to measure directly and indirectly the size, shape, and position of the organs. Displacement measurements can be made using sensors designed to exhibit a resistive, inductive, capacitive or piezoelectric change as a function of changes in position.

52 Resistive sensors - potentiometersMeasure linear and angular position Resolution a function of the wire construction Measure velocity and acceleration 2 to 500mm 10o and more

53 Resistive sensors – strain gagesDevices designed to exhibit a change in resistance as a result of experiencing strain to measure displacement in the order of nanometer. For a simple wire: A change in R will result from a change in  (resistively), or a change in L or A (dimension). The gage factor, G, is used to compare various strain-gage materials  Is Poisson’s ratio Semiconductor has larger G but more sensitive to temperature

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55 vo is zero when the bridge is balanced- that is when Wheatstone Bridge vo is zero when the bridge is balanced- that is when Show Proof in class If all resistor has initial value R0 then if R1 and R3 increase by R, and R2 and R4 decreases by R, then Show Proof in class

56 Initially before any pressure R1 = R4 and R3 = R2Unbonded strain gage: With increasing pressure, the strain on gage pair B and C is increased, while that on gage pair A and D is decreased. Initially before any pressure R1 = R4 and R3 = R2 Wheatstone Bridge A B D C Error in Fig. 2.2 legend: R1 = A, R2 = B, R3 = D, R4 = C

57 Bonded strain gage: - Metallic wire, etched foil, vacuum-deposited film or semiconductor is cemented to the strained surface - Rugged, cheap, low mass, available in many configurations and sizes - To offset temperature use dummy gage wire that is exposed to temperature but not to strain

58 Bonded strain gage terminology:Carrier (substrate + cover)

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60 Semiconductor Integrated Strain GagesPressure strain gages sensor with high sensitivity Integrated cantilever-beam force sensor

61 4 cm Clear plastic To patient Saline Flush valve IV tubing Gel Silicon chip Electrical cable Figure Isolation in a disposable blood-pressure sensor. Disposable blood pressure sensors are made of clear plastic so air bubbles are easily seen. Saline flows from an intravenous (IV) bag through the clear IV tubing and the sensor to the patient. This flushes blood out of the tip of the indwelling catheter to prevent clotting. A lever can open or close the flush valve. The silicon chip has a silicon diaphragm with a four-resistor Wheatstone bridge diffused into it. Its electrical connections are protected from the saline by a compliant silicone elastomer gel, which also provides electrical isolation. This prevents electric shock from the sensor to the patient and prevents destructive currents during defibrillation from the patient to the silicon chip.

62 b) venous-occlusion plethysmographyElastic-Resistance Strain Gages Extensively used in Cardiovascular and respiratory dimensional and volume determinations. As the tube stretches, the diameter decreases and the length increases, causing the resistance to increase b) venous-occlusion plethysmography c) arterial-pulse plethysmography Filled with a conductive fluid (mercury, conductive paste, electrolyte solution. Resistance = /cm, linear within 1% for 10% of maximal extension

63 Ampere’s Law: flow of electric current will create a magnetic field Inductive Sensors Ampere’s Law: flow of electric current will create a magnetic field Faraday’s Law: a magnetic field passing through an electric circuit will create a voltage i + + + v2  v1 v - - - N2 N1 

64 Inductive Sensors Ampere’s Law: flow of electric current will create a magnetic field Faraday’s Law: a magnetic field passing through an electric circuit will create a voltage Self-inductance Mutual inductance Differential transformer n = number of turns of coil G = geometric form factor  = effective magnetic permeability of the medium

65 LVDT : Linear variable differential transformer - full-scale displacement of 0.1 to 250 mm mV for a displacement of 0.01mm - sensitivity is much higher than that for strain gages Disadvantage requires more complex signal processing + - + _ (a) As x moves through the null position, the phase changes 180, while the magnitude of vo is proportional to the magnitude of x. (b) An ordinary rectifier-demodulator cannot distinguish between (a) and (b), so a phase-sensitive demodulator is required.

66 For a parallel plate capacitor:Capacitive Sensors Capacitive sensors For a parallel plate capacitor: 0 = dielectric constant of free space r = relative dielectric constant of the insulator A = area of each plate x = distance between plates Change output by changing r (substance flowing between plates), A (slide plates relative to each other), or x.

67 Sensitivity of capacitor sensor, K Sensitivity increases with increasing plate size and decreasing distance When the capacitor is stationary xo the voltage v1=E. A change in position x = x1 -xo produces a voltage vo = v1 – E. i + + Characteristics of capacitive sensors: High resolution (<0.1 nm) Dynamic ranges up to 300 µm (reduced accuracy at higher displacements) High long term stability (<0.1 nm / 3 hours) Bandwidth: 20 to 3 kHz

68 Piezoelectric SensorsMeasure physiological displacement and record heart sounds. Certain materials generate a voltage when subjected to a mechanical strain, or undergo a change in physical dimensions under an applied voltage. Uses of Piezoelectric External (body surface) and internal (intracardiac) phonocardiography Detection of Korotkoff sounds in blood- pressure measurements Measurements of physiological accelerations Provide an estimate of energy expenditure by measuring acceleration due to human movement.

69 (typically pC/N, a material property) k for Quartz = 2.3 pC/N Vo (typically pC/N, a material property) k for Quartz = 2.3 pC/N k for barium titanate = 140 pC/N To find Vo, assume system acts like a capacitor (with infinite leak resistance): Capacitor: For piezoelectric sensor of 1-cm2 area and 1-mm thickness with an applied force due to a 10-g weight, the output voltage v is 0.23 mV for quartz crystal 14 mV for barium titanate crystal.

70 Models of Piezoelectric SensorsPiezoelectric polymeric films, such as polyvinylidence fluoride (PVDF). Used for uneven surface and for microphone and loudspeakers.

71 Transfer Function of Piezoelectric SensorsView piezoelectric crystal as a charge generator: Rs: sensor leakage resistance Cs: sensor capacitance Cc: cable capacitance Ca: amplifier input capacitance Ra: amplifier input resistance Ra

72 Transfer Function of Piezoelectric SensorsConvert charge generator to current generator: Ra Current Ra Ks = K/C, sensitivity, V/m  = RC, time constant

73 Voltage-output response of a piezoelectric sensor to a step displacement x.Decay due to the finite internal resistance of the PZT The decay and undershoot can be minimized by increasing the time constant  =RC.

74 Example 2.1 C = 500 pF Rleak = 10 G Ra = 5 M  What is fc,low ?Current

75 High Frequency Equivalent CircuitRs

76 Temperature MeasurementThe human body temperature is a good indicator of the health and physiological performance of different parts of the human body. Temperature indicates: Shock by measuring the big-toe temperature Infection by measuring skin temperature Arthritis by measuring temperature at the joint Body temperature during surgery Infant body temperature inside incubators Temperature sensors type Thermocouples Thermistors Radiation and fiber-optic detectors p-n junction semiconductor (2 mV/oC)

77 Thermocouple Electromotive force (emf) exists across a junction of two dissimilar metals. Two independent effects cause this phenomena: 1- Contact of two unlike metals and the junction temperature (Peltier) 2- Temperature gradients along each single conductor (Lord Kelvin) E = f (T T22) T2  T1 T1 E = f(T1 –T2) A B Advantages of Thermocouple fast response (=1ms), small size (12 μm diameter), ease of fabrication and long-term stability Disadvantages Small output voltage, low sensitivity, need for a reference temperature

78 Thermocouple Empirical calibration data are usually curve-fitted with a power series expansion that yield the Seebeck voltage. T2  T1 T1 E = f(T1 –T2) A B T: Temperature in Celsius Reference junction is at 0 oC

79 Second law makes it possible for lead wire connectionsThermocouple Laws 1- Homogeneous Circuit law: A circuit composed of a single homogeneous metal, one cannot maintain an electric current by the application of heat alone. See Fig. 2.12b 2- Intermediate Metal Law: The net emf in a circuit consisting of an interconnection of a number of unlike metals, maintained at the same temperature, is zero. See Fig. 2.12c Second law makes it possible for lead wire connections 3- Successive or Intermediate Temperatures Law: See Fig. 2.12d The third law makes it possible for calibration curves derived for a given reference-junction temperature to be used to determine the calibration curves for another reference temperature. T1 T2 T3

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81 Thermoelectric Sensitivity For small changes in temperature: T2 T1 E = f(T1 –T2) A B Differentiate above equation to find , the Seebeck coefficient, or thermoelectric sensitivity. Generally in the range of V/oC at 20 oC.

82 Thermistors Thermistors are semiconductors made of ceramic materials whose resistance decreases as temperature increases. Advantages Small in size (0.5 mm in diameter) Large sensitivity to temperature changes (-3 to -5% /oC) Blood velocity Temperature differences in the same organ Excellent long-term stability characteristics (R=0.2% /year) Disadvantages -Nonlinear -Self heating -Limited range

83 Circuit Connections of ThermistorsBridge Connection to measure voltage R1 R2 R3 Rt va vb V Amplifier Connection to measure currents

84 Thermistors Resistance Relationship between Resistance and Temperature at zero-power resistance of thermistor. 1000 100  = material constant for thermistor, K (2500 to 5000 K) To = standard reference temperature, K To = K = 20C = 68F 10 1 Resistance ratio, R/R25º C 0.1 Temperature coefficient  0.01 0.001  is a nonlinear function of temperature  Temperature, ° C (a) Figure (a) Typical thermistor zero-power resistance ratio-temperature characteristics for various materials.

85 Voltage-Versus-Current CharacteristicsThe temperature of the thermistor is that of its surroundings. However, above specific current, current flow generates heat that make the temperature of the thermistor above the ambient temperature. 0.1 1.0 10 100 0.10 Water Air 0.1 mW 1 mW 10 mW 100 mW 1 W 100  1 k 10 k 100 k  1 M  A C B Current, mA (b) 10.0 100.0 Voltage, V Figure (b) Thermistor voltage-versus-current characteristic for a thermistor in air and water. The diagonal lines with a positive slope give linear resistance values and show the degree of thermistor linearity at low currents. The intersection of the thermistor curves and the diagonal lines with the negative slope give the device power dissipation. Point A is the maximal current value for no appreciable self-heat. Point B is the peak voltage. Point C is the maximal safe continuous current in air.

86 Radiation ThermometryThe higher the temperature of a body the higher is the electromagnetic radiation (EM). Electromagnetic Radiation Transducers - Convert energy in the form of EM radiation into an electrical current or potential, or modify an electrical current or potential. Medical thermometry maps the surface temperature of a body with a sensitivity of a few tenths of a Kelvin. Application Breast cancer, determining location and extent of arthritic disturbances, measure the depth of tissue destruction from frostbite and burns, detecting various peripheral circulatory disorders (venous thrombosis, carotid artery occlusions)

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88 Radiation ThermometrySources of EM radiation: Acceleration of charges can arise from thermal energy. Charges movement cause the radiation of EM waves. The amount of energy in a photon is inversely related to the wavelength: Thermal sources approximate ideal blackbody radiators: Blackbody radiator: an object which absorbs all incident radiation, and emits the maximum possible thermal radiation (0.7 m to 1mm).

89 Power Emitted by a Blackbody Stefan-Boltzman lawPower emitted at a specific wavelength: 100% m= m 80 0.003 60 0.002 Spectral radient emittance, W-cm-2·mm-1 40 Unit : W/cm2. m C1 = 3.74x104 (W. m4/cm2) C2 = 1.44x104 (m. K) T = blackbody temperature, K  = emissivity (ideal blackbody = 1) % Total power 0.001 20 T = 300 K 5 10 15 20 25 Wavelength, m (a) Spectral radiant emittance versus wavelength for a blackbody at 300 K on the left vertical axis; percentage of total energy on the right vertical axis. Wavelength for which W is maximum: m varies inversely with T - Wien’s displacement law

90 Power Emitted by a Blackbody Stefan-Boltzman law5 0.001 0.002 0.003 10 Wavelength, m 15 20 T = 300 K m= m 25 40 60 80 100% % Total power Spectral radient emittance, W-cm-2·mm-1 Total radiant power: 80% of the total radiant power is found in the wavelength band from 4 to 25 m Unit : W/cm2. m

91 Thermal Detector Specifications1 10 50 100 Fused silica Sapphire Arsenic trisulfide Thallium bromide iodine Wavelength, m Infrared Instrument Lens Properties; pass wavelength > 1 m high sensitivity to the weak radiated signal Short response Respond to large bandwidth Thermal Detectors -Law sensitivity Respond to all wavelength Photon (Quantum) Detector -higher sensitivity -Respond to a limited wavelength Fig. a 1 2 3 Wavelength, m Indium antimonide (InSb) (photovoltaic) Lead sulfide (PbS) All thermal detectors 20 60 100 4 5 6 7 8 Fig. a) Spectral transmission for a number of optical materials. (b) Spectral sensitivity of photon and thermal detectors. Fig. b

92 Figure 2.15 Stationary chopped-beam radiation thermometerRadiation Thermometer System Figure 2.15 Stationary chopped-beam radiation thermometer

93 Application of Radiation ThermometerMeasuring the core body temperature of the human by measuring the magnitude of infrared radiation emitted from the tympanic membrane and surrounding ear canal. Response time is 0.1 second Accuracy of 0.1 oC

94 Fiber-Optic Temperature SensorsSmall and compatible with biological implantation. Nonmetallic sensor so it is suitable for temperature measurements in a strong electromagnetic heating field. Gallium Arsenide (GaAs) semiconductor temperature probe. The amount of power absorbed increases with temperature

95 1- Clinical-chemistry lab (analyze sample of blood and tissue) Optical Measurements Applications: 1- Clinical-chemistry lab (analyze sample of blood and tissue) 2- Cardiac Catheterization (measure oxygen saturation of hemoglobin and cardiac output) Components: Sources, filters, and detectors. General block diagram of an optical instrument. (b) Highest efficiency is obtained by using an intense lamp, lenses to gather and focus the light on the sample in the cuvette, and a sensitive detector. (c) Solid-state lamps and detectors may simplify the system.

96 Coiled filaments to increase emissivity and efficiency. Radiation Sources 1- Tungsten Lamps Coiled filaments to increase emissivity and efficiency. - Ribbon filaments for uniform radiation Tungsten-halogen lamps have iodine or bromine to maintain more than 90% of their initial radiant. Figure 2.18 Spectral characteristics of sources, (a) Light sources, Tungsten (W) at 3000 K has a broad spectral output. At 2000 K, output is lower at all wavelengths and peak output shifts to longer wavelengths.

97 Radiation Sources 2- ARC Discharges Low-pressure lamp: Fluorescent lamp filled with Argon-Mercury (Ar-Hg) mixture. Accelerated electron hit the mercury atom and cause the radiation of 250 nm (5 eV) wavelength which is absorbed by phosphor. Phosphor will emits light of longer visible wavelengths. Fluorescent lamp has low radiant so it is not used for optical instrument, but can be turned on in 20 sec and used for tachistoscope to provide brief stimuli to the eye. - High pressure lamp: mercury, sodium, xenon lamps are compact and can provide high radiation per unit area. Used in optical instruments.

98 3- Light-Emitting Diodes (LED) Radiation Sources 3- Light-Emitting Diodes (LED) A p-n junction devices that are optimized to radiant output. GaAs has a higher band gap and radiate at 900 nm. Switching time 10 nsec. GaP LED has a band gap of 2.26 eV and radiate at 700 nm GaAsP absorb two photons of 940 nm wavelength and emits one photon of 540 nm wavelength. Advantages of LED: compact, rugged, economical, and nearly monochromatic. Figure 2.18 Spectral characteristics of sources, (a) Light-emitting diodes yield a narrow spectral output with GaAs in the infrared, GaP in the red, and GaAsP in the green.

99 4- Laser (Light Amplification by Stimulated Emission of Radiation) Radiation Sources 4- Laser (Light Amplification by Stimulated Emission of Radiation) -He-Ne lasers operate at 633 nm with 100 mW power. Argon laser operates at 515 nm with the highest continuous power level with 1-15 W power. CO2 lasers provide W of continuous wave output power. Ruby laser is a solid state lasers operate in pulsed mode and provide 693 nm with 1-mJ energy. The most medical use of the laser is to mend tear in the retina. Figure 2.18 Spectral characteristics of sources, (a) Monochromatic outputs from common lasers are shown by dashed lines: Ar, 515 nm; HeNe, 633 nm; ruby, 693 nm; Nd, 1064 nm

100 Optical Filters Optical filters are used to control the distribution of radiant power or wavelength. Power Filters Glass partially silvered: most of power are reflected Carbon particles suspended in plastic: most of power are absorbed Two Polaroid filters: transmit light of particular state of polarization Wavelength Filters -Color Filters: colored glass transmit certain wavelengths -Gelatin Filters: a thin film of organic dye dried on a glass (Kodak 87) or combining additives with glass when it is in molten state (corning 5-56 ). Interference Filters: Depositing a reflective stack of layers on both sides of a thicker spacer layer. LPF, BPF, HPF of bandwidth from 0.5 to 200nm. Diffraction grating Filters: produce a wavelength spectrum.

101 Optical Filters Figure 2.18 Spectral characteristics of filters (b) Filters. A Corning 5-65 glass filter passes a blue wavelength band. A Kodak 87 gelatin filter passes infrared and blocks visible wavelengths. Germanium lenses pass long wavelengths that cannot be passed by glass. Hemoglobin Hb and oxyhemoglobin HbO pass equally at 805 nm and have maximal difference at 660 nm. Optical method for measuring fat in the body (fat absorption 930 nm Water absorption 970 nm

102 Classifications of Radiation Sensors Thermal Sensors: absorbs radiation and change the temperature of the sensor. -Change in output could be due to change in the ambient temperature or source temperature. -Sensitivity does not change with wavelength -Slow response Example: Pyroelectric sensor: absorbs radiation and convert it to heat which change the electric polarization of the crystals. Quantum Sensors: absorb energy from individual photons and use it to release electrons from the sensor material. -sensitive over a restricted band of wavelength -Fast response -Less sensitive to ambient temperature Example: Eye, Phototube, photodiode, and photographic emulsion.

103 Photoemissive SensorsPhototube: have photocathode coated with alkali metals. A radiation photon with energy cause electron to jump from cathode to anode. Photon energies below 1 eV are not large enough to overcome the work functions, so wavelength over 1200nm cannot be detected. Photomultiplier An incoming photon strikes the photocathode and liberates an electron. This electron is accelerated toward the first dynode, which is 100 V more positive than the cathode. The impact liberates several electrons by secondary emission. They are accelerated toward the second dynode, which is 100 V more positive than the first dynode, This electron multiplication continues until it reaches the anode, where currents of about 1 A flow through RL. Time response < 10 nsec

104 Photoconductive CellsPhotoresistors: a photosensitive crystalline materials such as cadmium Sulfide (CdS) or lead sulfide (PbS) is deposited on a ceramic substance. The resistance decrease of the ceramic material with input radiation. This is true if photons have enough energy to cause electron to move from the valence band to the conduction band.

105 Photojunction SensorsPhotojunction sensors are formed from p-n junctions and are usually made of silicon. If a photon has enough energy to jump the band gap, hole-electron pairs are produced that modify the junction characteristics. Photodiode: With reverse biasing, the reverse photocurrent increases linearly with an increase in radiation. Phototransistor: radiation generate base current which result in the generation of a large current flow from collector to emitter. Response time = 10 microsecond Figure 2.22 Voltage-current characteristics of irradiated silicon p-n junction. For 0 irradiance, both forward and reverse characteristics are normal. For 1 mW/cm2, open-circuit voltage is 500 mV and short-circuit current is 8 A.

106 Photovoltaic Sensors Photovoltaic sensors is a p-n junction where the voltage increases as the radiation increases. Figure 2.18 Spectral characteristics of detectors, (c) Detectors. The S4 response is a typical phototube response. The eye has a relatively narrow response, with colors indicated by VBGYOR. CdS plus a filter has a response that closely matches that of the eye. Si p-n junctions are widely used. PbS is a sensitive infrared detector. InSb is useful in far infrared. Note: These are only relative responses. Peak responses of different detectors differ by 107.

107 S= relative source output; F= relative filter transmission Optical Combinations Total effective irradiance, is found by breaking up the spectral curves into many narrow bands and then multiplying each together and adding the resulting increments. S= relative source output; F= relative filter transmission D= relative sensor responsivity Figure 2.18 Spectral characteristics of combinations thereof (d) Combination. Indicated curves from (a), (b), and (c) are multiplied at each wavelength to yield (d), which shows how well source, filter, and detector are matched.

108 Strain Gages (Bounded and Unbonded) (Niraj) Project1 (Sensors) Resistive Sensors Strain Gages (Bounded and Unbonded) (Niraj) Blood Pressure Sensors (KJ) Inductive Sensor (LVDT) Capacitive Sensors Piezoelectric Sensors Temperature Sensors (Thermocouple, Thermistors) Radiation Thermometry (Sultana) Infrared Thermometer Sensors Fiber Optic temperature Sensors (HL) Radiation Sources (ARC, LEDs) (Jeremiah) Thermal Sensors (Kendal) Quantum Sensors Photoemissive Sensors Photoconductive cells (Kelli) Photojunction Sensors Photovoltaic Sensors

109 Chapter 3-Webster Amplifiers and Signal Processing

110 Applications of Operational Amplifier In Biological Signals and SystemsThe three major operations done on biological signals using Op-Amp: Amplifications and Attenuations DC offsetting: add or subtract a DC Filtering: Shape signal’s frequency content

111 Ideal Op-Amp Most bioelectric signals are small and require amplifications Figure 3.1 Op-amp equivalent circuit. The two inputs are 1 and  2. A differential voltage between them causes current flow through the differential resistance Rd. The differential voltage is multiplied by A, the gain of the op amp, to generate the output-voltage source. Any current flowing to the output terminal vo must pass through the output resistance Ro.

112 Inside the Op-Amp (IC-chip)20 transistors 11 resistors 1 capacitor

113 Ideal Characteristics1- A =  (gain is infinity) 2- Vo = 0, when v1 = v2 (no offset voltage) 3- Rd =  (input impedance is infinity) 4- Ro = 0 (output impedance is zero) 5- Bandwidth =  (no frequency response limitations) and no phase shift

114 Two Basic Rules Rule 1 When the op-amp output is in its linear range, the two input terminals are at the same voltage. Rule 2 No current flows into or out of either input terminal of the op amp.

115 Inverting Amplifier 10 V (b) i o Slope = -Rf / Ri -10 V Ri i o i Rf +  (a) Figure 3.3 (a) An inverting amplified. Current flowing through the input resistor Ri also flows through the feedback resistor Rf . (b) The input-output plot shows a slope of -Rf / Ri in the central portion, but the output saturates at about ±13 V.

116 Summing Amplifier Rf R1 1  R2 o 2 +

117 Example 3.1 The output of a biopotential preamplifier that measures the electro-oculogram is an undesired dc voltage of ±5 V due to electrode half-cell potentials, with a desired signal of ±1 V superimposed. Design a circuit that will balance the dc voltage to zero and provide a gain of -10 for the desired signal without saturating the op amp. +10 Ri Rf i 10 k 100 k i  i + b /2 +15V Rb o Voltage, V 20 k Time 5 k + v b -15 V -10 o (a) (b)

118 Follower ( buffer) o iUsed as a buffer, to prevent a high source resistance from being loaded down by a low-resistance load. In another word it prevents drawing current from the source.  o i +

119 Noninverting AmplifierRi Rf Slope = (Rf + Ri )/ Ri -10 V 10 V i - o i -10 V +

120 Differential AmplifiersDifferential Gain Gd R3 R4 v3 R3 v4 vo Common Mode Gain Gc For ideal op amp if the inputs are equal then the output = 0, and the Gc =0. No differential amplifier perfectly rejects the common-mode voltage. R4 Common-mode rejection ratio CMMR Typical values range from 100 to 10,000 Disadvantage of one-op-amp differential amplifier is its low input resistance

121 Instrumentation AmplifiersDifferential Mode Gain Instrumentation Amplifiers Advantages: High input impedance, High CMRR, Variable gain

122 Comparator – No Hysteresisv2 +15 -15 v1 > v2, vo = -13 V v1 < v2, vo = +13 V o i ref 10 V -10 V i o  + R1 R2 ref If (vi+vref) > 0 then vo = -13 V else vo = +13 V R1 will prevent overdriving the op-amp

123 Comparator – With HysteresisReduces multiple transitions due to mV noise levels by moving the threshold value after each transition. o i - ref 10 V -10 V With hysteresis i o  + R1 R2 R3 ref Width of the Hysteresis = 4VR3

124 Rectifier 10 V (b) -10 V o i  + (a) D3 R o= i D2 D1 D4 xR (1-x)R x xR (1-x)R v o  D2 i + (a) Full-wave precision rectifier: a) For i > 0, D2 and D3 conduct, whereas D1 and D4 are reverse-biased. Noninverting amplifier at the top is active

125 Rectifier  + (a) D3 R o= i D2 D1 D4 xR (1-x)R x xRi R i v o  D4 + (b) 10 V (b) -10 V o i Full-wave precision rectifier: b) For i < 0, D1 and D4 conduct, whereas D2 and D3 are reverse-biased. Inverting amplifier at the bottom is active

126 One-Op-Amp Full Wave RectifierD v o i  + Ri = 2 k Rf = 1 k RL = 3 k For i < 0, the circuit behaves like the inverting amplifier rectifier with a gain of For i > 0, the op amp disconnects and the passive resistor chain yields a gain of +0.5.

127 Logarithmic AmplifiersUses of Log Amplifier Multiply and divide variables Raise variable to a power Compress large dynamic range into small ones Linearize the output of devices (a) Rf Ic Rf /9 o Ri i  + VBE Figure 3.8 (a) A logarithmic amplifier makes use of the fact that a transistor's VBE is related to the logarithm of its collector current. For range of Ic equal 10-7 to 10-2 and the range of vo is -.36 to V.

128 Logarithmic AmplifiersVBE Rf /9 (b) 10 V -10 V v o i 1 10 Ic VBE 9VBE Rf Ri i  o + (a) Figure 3.8 (a) With the switch thrown in the alternate position, the circuit gain is increased by 10. (b) Input-output characteristics show that the logarithmic relation is obtained for only one polarity; 1 and 10 gains are indicated.

129 Integrators for f < fcA large resistor Rf is used to prevent saturation

130 Integrators Figure 3.9 A three-mode integrator With S1 open and S2 closed, the dc circuit behaves as an inverting amplifier. Thus o = ic and o can be set to any desired initial conduction. With S1 closed and S2 open, the circuit integrates. With both switches open, the circuit holds o constant, making possible a leisurely readout.

131 Example 3.2 The output of the piezoelectric sensor may be fed directly into the negative input of the integrator as shown below. Analyze the circuit of this charge amplifier and discuss its advantages. isC = isR = 0 vo = -vc R + FET Piezo-electric sensor   C is isR isC dqs/ dt = is = K dx/dt Long cables may be used without changing sensor sensitivity or time constant.

132 Differentiators Figure 3.11 A differentiator The dashed lines indicate that a small capacitor must usually be added across the feedback resistor to prevent oscillation.

133 Active Filters- Low-Pass FilterCf Gain = G = Ri Rf i  o + (a) |G| Rf/Ri 0.707 Rf/Ri freq fc = 1/2RiCf Active filters (a) A low-pass filter attenuates high frequencies

134 Active Filters (High-Pass Filter)Ci Ri Rf  i Gain = G = o + |G| (b) Rf/Ri 0.707 Rf/Ri freq fc = 1/2RiCf Active filters (b) A high-pass filter attenuates low frequencies and blocks dc.

135 Active Filters (Band-Pass Filter)Cf Ci Rf Ri  i o + |G| (c) Rf/Ri 0.707 Rf/Ri freq fcL = 1/2RiCi fcH = 1/2RfCf Active filters (c) A bandpass filter attenuates both low and high frequencies.

136 Frequency Response of op-amp and AmplifierOpen-Loop Gain Compensation Closed-Loop Gain Loop Gain Gain Bandwidth Product Slew Rate

137 Offset Voltage and Bias CurrentRead section 3.12 Nulling, Drift, Noise Read section and 3.13 Differential bias current, Drift, Noise

138 Input and Output Resistance+  Rd ii Ro RL CL io Ad d o i Typical value of Rd = 2 to 20 M Typical value of Ro = 40 

139 Phase Modulator for Linear variable differential transformer LVDT+ -

140 Phase Modulator for Linear variable differential transformer LVDT+ -

141 Phase-Sensitive DemodulatorUsed in many medical instruments for signal detection, averaging, and Noise rejection

142 The Ring Demodulator vc  2viIf vc is positive then D1 and D2 are forward-biased and vA = vB. So vo = vDB If vc is negative then D3 and D4 are forward-biased and vA = vc. So vo = vDC vc  2vi

143 Chapter 4-Webster The Origin of BiopotentialsNote: Some of the figures in this presentation have been taken from reliable websites in the internet and textbooks.

144 Bioelectric Signals Bioelectrical potential is a result of electrochemical activity across the membrane of the cell. Bioelectrical signals are generated by excitable cells such as nervous, muscular, and glandular cells. The resting potential of the cell is -40 to -90 mV relative to the outside and +60 mV during action potential. Volume conductor electric field is an electric field generated by many excitable cells of the specific organ such as the heart. Typical types of bioelectric signals Electrocardiogram (ECG, EKG) Electroencephalogram (EEG) Electromyogram (EMG) Electroretinogram (ERG)

145 Bioelectric Signals L: latent period= transmission time from stimulus to recording site. Potential inside cells -40 to -90 mV relative to the outside. Cell membrane is lipoprotein complex that is impermeable to intracellular protein and other organic anions (A-)

146 Frog skeletal muscle membrane Frog skeletal muscle membrane The Resting State Membrane at resting state is slightly permeable to Na+ and freely permeable to K+ and Cl- permeability of potassium PK is 50 to 100 times larger than the permeability to sodium ion PNa. 2.5 mmol/liter of K+ 140 mmol/liter of K+ 2.5 mmol/liter of K+ 140 mmol/liter of K+ Cl- K+ Cl- K+ Electric Field + - + - External media Internal media External media Internal media Frog skeletal muscle membrane Frog skeletal muscle membrane Diffusional force > electrical force Diffusional force = electrical force

147 Sodium-Potassium PumpKeeping the cell at resting state requires active transport of ionic species against their normal electrochemical gradients. Sodium-potassium pump is an active transport that transports Na+ out of the cell and K+ into the cell in ration 3Na+:2K+ Energy for the pump is provided by a cellular energy adenosine triphosphate (ATP) 2.5 mmol/liter of K+ 140 mmol/liter of K+ 2K+ 3Na+ + - + - Electric Field External media Internal media Frog skeletal muscle membrane

148 Equilibrium Potential- Nernst EquationAt 37 oC Where n is the valence of K+. E: Equilibrium transmembrane resting potential, net current is zero PM : permeability coefficient of the membrane for ionic species M [M]i and [M]o : the intracellular and extracellular concentrations of M in moles/ liter R: Universal gas constant (8.31 j/mol.k) T: Absolute temperature in K F: Faraday constant (96500 c/equivalent)

149 Example 4.1 For the frog skeletal muscle, typical values for the intracellular and extracellular concentrations for the major ion species (in millimoles per liter) are as follows. Species Intracellular Extracellular Na K Cl Assuming room temperature (20 oC) and typical values of permeability coefficient for the frog skeletal muscle (PNa = 2*10-8 cm/s, Pk = 2*10-6 cm/s, and PCl = 4*10-6 cm/s), calculate the equilibrium resting potential for this membrane, using the Goldman equation.

150 The Active State Membrane at resting state is polarized (more negative inside the cell) Depolarization : lessening the magnitude of cell polarization by making inside the cell less negative. Hyperpolarization : increasing the magnitude of cell polarization by making inside the cell more negative. A stimulus that depolarize the cell to a potential higher than the threshold potential causes the cell to generate an action potential. Action Potential: - Rate: 1000 action potential per second for nerve - All-or-none - v = 120 mV for nerve

151 Action Potential External media Internal media 2.5 mmol/liter of K+If stimulus depolarize the cell such that Vcell > Vthreshold an action potential is generated. External media Internal media 2.5 mmol/liter of K+ 140 mmol/liter of K+ Na+ + - Electric Field + - K+ - + Electric Field - +

152 Action Potential Absolute refractory period: membrane can not respond to any stimulus. Relative refractory period: membrane can respond to intense stimulus.

153 Action Potential Action potential travel at one direction.Local closed (solenoidal) lines of current flow Repolarized membrane Axon Resting External medium +  Active region Depolarized Direction of propagation Schwann Cell Node of Ranvier Myelin sheath Active node Periaxonal space Axon +  Myelination reduces leakage currents and improve transmission rate by a factor of approximately 20.

154 Diagram of network equivalent circuit of a small length (z) of an unmyelinated nerve fiber or a skeletal muscle fiber The membrane proper is characterized by specific membrane capacitance Cm (F/cm2) and specific membrane conductances gNa, gK, and gCl in mS/cm2 (millisiemens/cm2). Here an average specific leakage conductance is included that corresponds to ionic current from sources other than Na+ and K+ (for example, Cl-). This term is usually neglected. The cell cytoplasm is considered simply resistive, as is the external bathing medium; these media may thus be characterized by the resistance per unit length ri and ro (/cm), respectively. Here im is the transmembrane current per unit length (A/cm), and i and o are the internal and external potentials  at point z, respectively.

155 Volume Conductor FieldsVolume conductor fields is an electric field generated by active cell (current source) or cells immersed in a volume conductor medium of resistivity  such as the body fluids. Potential Waveform at the outer surface of membrane for monophasic action potential: 1- triphasic in nature 2- greater spatial extent than the action potential 3- much smaller in peak to peak magnitude 4- relatively constant in propagation along the excited cell. - Potential in the extracellular medium of a single fiber fall off exponentially in magnitude with increasing radial distance from the fiber (potential zero within fifteen fiber radii) - Potential depends on medium Properties. Local closed (solenoidal) lines of current flow Repolarized membrane Axon Resting External medium +  Active region Depolarized Direction of propagation

156 Volume Conductor FieldsThe extracellular field of an active nerve trunk with its thousands of component nerve fibers simultaneously activated is similar to the field of a single fiber. Figure 4.5 Extracellular field potentials (average of 128 responses) were recorded at the surface of an active (1-mm-diameter) frog sciatic nerve in an extensive volume conductor. The potential was recorded with (a) both motor and sensory components excited (Sm + Ss), (b) only motor nerve components excited (Sm), and (c) only sensory nerve components excited (Ss). Sensory branch Motor branch

157

158 Peripheral Nervous SystemSpinal nervous system is functionally organized on the basis of what is called the reflex arc: A sense organ: (ear-sound, eye-light, skin-temperature) A sensory nerve: (transmit information to the CNS) The CNS: serves as a central integrating station Motor nerve: communication link between CNS and peripheral muscle Effector organ: skeletal muscle fibers

159 Example of reflex arc Example of reflex arc

160 (Feedback) Schematic diagram of a muscle-length control system for a peripheral muscle (biceps) (a) Anatomical diagram of limb system, showing interconnections. (b) Block diagram of control system.

161 Junctional TransmissionSynapses: intercommunicating links between neurons Neuromuscular junctions: communicating links between neurons and muscle fibers at end-plate region. Neuromuscular junction (20nm thickness) release neurotransmitter substance Acetylcholine (Ach) Time delay due to junction is 0.5 to 1 msec Excitation-contraction time delay due to muscle contraction Neuron Muscle end-plate region At high stimulation rates, the mechanical response fuse into one continuous contraction called a tetanus (mechanical response summates).

162 Neuromuscular junction

163 Electroneurogram (ENG)Recording the field potential of an excited nerve. Neural field potential is generated by - Sensory component - Motor component Parameters for diagnosing peripheral nerve disorder Conduction velocity Latency Characteristic of field potentials evoked in muscle supplied by the stimulated nerve (temporal dispersion) Amplitude of field potentials of nerve fibers < extracellular potentials from muscle fibers.

164 Conduction Velocity of a NerveV(t) S1 S2 +  +  R Reference D Muscle S2 V(t) D L2 t Velocity = u = S1 L1L2 V(t) 1 mV L1 2 ms Figure 4.7 Measurement of neural conduction velocity via measurement of latency of evoked electrical response in muscle. The nerve was stimulated at two different sites a known distance D apart.

165 Field Potential of Sensory NervesExtracellular field response from the sensory nerves of the median or ulnar nerves To excite the large, rapidly conducting sensory nerve fibers but not small pain fibers or surrounding muscle, apply brief, intense stimulus ( square pulse with amplitude 100-V and duration sec). To prevent artifact signal from muscle movement position the limb in a comfortable posture. Figure 4.8 Sensory nerve action potentials evoked from median nerve of a healthy subject at elbow and wrist after stimulation of index finger with ring electrodes. The potential at the wrist is triphasic and of much larger magnitude than the delayed potential recorded at the elbow. Considering the median nerve to be of the same size and shape at the elbow as at the wrist, we find that the difference in magnitude and waveshape of the potentials is due to the size of the volume conductor at each location and the radial distance of the measurement point from the neural source.

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167

168 Reflexly Evoked Field PotentialsSome times when a peripheral nerve is stimulated, a two evoked potentials are recorded in the muscle the nerve supplies. The time difference between the two potentials determined by the distance between the stimulus and the muscle. Stimulated nerve: posterior tibial nerve Muscle: gastrocnemius

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170 Reflexly Evoked Field PotentialsLow intensity stimulus stimulate only the large sensory fibers that conduct toward the CNS. No M wave Medium intensity stimulus stimulate smaller motor fibers in addition to the large sensory fibers. Motor fibers produce a direct muscle response the M wave. With strong stimuli, the excited motor fibers are in their refractory period so only the M wave is produced. Figure 4.9 The H reflex The four traces show potentials evoked by stimulation of the medial popliteal nerve with pulses of increasing magnitude (the stimulus artifact increases with stimulus magnitude). The later potential or H wave is a low-threshold response, maximally evoked by a stimulus too weak to evoke the muscular response (M wave). As the M wave increases in magnitude, the H wave diminishes.

171 Electromyogram (EMG) Skeletal muscle is organized functionally on the basis of the single motor unit (SMU). SMU is the smallest unit that can be activated by a volitional effort where all muscle fibers are activated synchronously. SMU may contain 10 to 2000 muscle fibers, depending on the location of the muscle. Factors for muscle varying strength Number of muscle fibers contracting within a muscle Tension developed by each contracting fiber

172 Muscle Fiber (Cell)

173 Figure Diagram of a single motor unit (SMU), which consists of a single motoneuron and the group of skeletal muscle fibers that it innervates. Length transducers [muscle spindles, Figure 4.6(a)] in the muscle activate sensory nerve fibers whose cell bodies are located in the dorsal root ganglion. These bipolar neurons send axonal projections to the spinal cord that divide into a descending and an ascending branch. The descending branch enters into a simple reflex arc with the motor neuron, while the ascending branch conveys information regarding current muscle length to higher centers in the CNS via ascending nerve fiber tracts in the spinal cord and brain stem. These ascending pathways are discussed in Section 4.8.

174 Field potential of the active fibers of an SMU 1- triphasic form Electromyogram (EMG) Field potential of the active fibers of an SMU 1- triphasic form 2- duration 3-15 msec 3- discharge rate varies from 6 to 30 per second 4- Amplitude range from 20 to 2000 V Surface electrode record field potential of surface muscles and over a wide area. Monopolar and bipolar insertion-type needle electrode can be used to record SMU field potentials at different locations. The shape of SMU potential is considerably modified by disease such as partial denervation.

175 Figure 4.11 Motor unit action potentials from normal dorsal interosseus muscle during progressively more powerful contractions. In the interference pattern (c ), individual units can no longer be clearly distinguished. (d) Interference pattern during very strong muscular contraction. Time scale is 10 ms per dot.

176 Electroretinogram (ERG)ERG is a recording of the temporal sequence of changes in potential in the retina when stimulated with a brief flash of light. Aqueous humor Glaucoma High pressure A transparent contact lens contains one electrode and the reference electrode can be placed on the right temple.

178 Source of Retinal PotentialThere are more photoreceptors than ganglion cells so there is a convergence pattern. Many photoreceptors terminate into one bipolar cell and many bipolar cells terminate into one ganglion cell. The convergence rate is greater at peripheral parts of the retina than at the fovea. Rod (10 million) is for vision in dim light and cone (3 million) is for color vision in brighter light.

179 Electroretinogram (ERG)The a-wave, sometimes called the "late receptor potential," reflects the general physiological health of the photoreceptors in the outer retina. In contrast, the b-wave reflects the health of the inner layers of the retina, including the ON bipolar cells and the Muller cells (Miller and Dowling, 1970). Two other waveforms that are sometimes recorded in the clinic are the c-wave originating in the pigment epithelium (Marmor and Hock, 1982) and the d-wave indicating activity of the OFF bipolar cells (see Figure 3).

181 Electro-Oculogram (EOG)EOG is the recording of the corneal-retinal potential to determine the eye movement. By placing two electrodes to the left and the right of the eye or above and below the eye one can measure the potential between the two electrode to determine the horizontal or vertical movement of the eye. The potential is zero when the gaze is straight ahead. Applications 1- Sleep and dream research, 2- Evaluating reading ability and visual fatigue.

182 Bionic Eyes

183 Electrocardiogram (ECG)Blood (poor with oxygen) flows from the body to the right atrium and then to the right ventricle. The right ventricle pump the blood to the lung. Blood (rich with oxygen) flows from the lung into the left atrium and then to the left ventricle. The left ventricle pump the blood to the rest of the body. Diastole: is the resting or filling phase (atria chamber) of the heart cycle. Systole: is the contractile or pumping phase (ventricle chamber) of the heart cycle. The electrical events is intrinsic to the heart itself. See website below for the animation of the heart.

184 Electrocardiogram (ECG)Distribution of specialized conductive tissues in the atria and ventricles, showing the impulse-forming and conduction system of the heart. The rhythmic cardiac impulse originates in pacemaking cells in the sinoatrial (SA) node, located at the junction of the superior vena cava and the right atrium. Note the three specialized pathways (anterior, middle, and posterior internodal tracts) between the SA and atrioventricular (AV) nodes. Bachmann's bundle (interatrial tract) comes off the anterior internodal tract leading to the left atrium. The impulse passes from the SA node in an organized manner through specialized conducting tracts in the atria to activate first the right and then the left atrium. Passage of the impulse is delayed at the AV node before it continues into the bundle of His, the right bundle branch, the common left bundle branch, the anterior and posterior divisions of the left bundle branch, and the Purkinje network. The right bundle branch runs along the right side of the interventricular septum to the apex of the right ventricle before it gives off significant branches. The left common bundle crosses to the left side of the septum and splits into the anterior division (which is thin and long and goes under the aortic valve in the outflow tract to the anterolateral papillary muscle) and the posterior division (which is wide and short and goes to the posterior papillary muscle lying in the inflow tract).

185 SA node activates first the right and then the left atrium.AV node delays a signal coming from the SA node before it distribute it to the Bundle of His. Bundle of His and Purkinie fibers activate the right and left ventricles A typical QRS amplitude is 1-3 mV The P-wave shows the heart's upper chambers (atria) contracting (depol.) The QRS complex shows the heart's lower chambers (ventricles) contracting The T-wave shows the heart's lower chambers (ventricles) relaxing (repol.) The U-wave believed to be due repolarization of ventricular papillary muscles. P-R interval is caused by delay in the AV node S-T segment is related to the average duration of the plateau regions of the individual ventricular cells.

186 Myofibrils Centroid NucleiSteps of action potential of the ventricular cell -Prior to excitation the resting potential is -90 mV -Rapid Depolarization at a rate 150 V/s -Initial rapid repolarization that leads to a fixed depolarization level for 200 t0 300 msec -Final repolarization phase that restore membrane potential to the resting level for the remainder of the cardiac cycle Myofibrils Centroid Nuclei The cellular architecture of myocardial fibers.

187 Isochronous lines of ventricular activation of the human heart Note the nearly closed activation surface at 30 ms into the QRS complex.

188 Figure 4.16 The electrocardiography problem Points A and B are arbitrary observation points on the torso, RAB is the resistance between them, and RT1 , RT2 are lumped thoracic medium resistances. The bipolar ECG scalar lead voltage is A  B, where these voltages are both measured with respect to an indifferent reference potential.

189 Heart Block (dysfunctional His Bundle)Figure 4.17 Atrioventricular block (a) Complete heart block. Cells in the AV node are dead and activity cannot pass from atria to ventricles. Atria and ventricles beat independently, ventricles being driven by an ectopic (other-than-normal) pacemaker. (B) AV block wherein the node is diseased (examples include rheumatic heart disease and viral infections of the heart). Although each wave from the atria reaches the ventricles, the AV nodal delay is greatly increased. This is first-degree heart block. 60 to 70 bps 30 to 45 bps - When one branch of the bundle of His is interrupted, then the QRS complexes are prolonged while the heart rate is normal.

190 Arrhythmias A portion of the myocardium sometimes becomes “irritable” and discharge independently. Figure 4.18 Normal ECG followed by an ectopic beat An irritable focus, or ectopic pacemaker, within the ventricle or specialized conduction system may discharge, producing an extra beat, or extrasystole, that interrupts the normal rhythm. This extrasystole is also referred to as a premature ventricular contraction (PVC).

191 Figure 4. 19 (a) Paroxysmal tachycardiaFigure (a) Paroxysmal tachycardia. An ectopic focus may repetitively discharge at a rapid regular rate for minutes, hours, or even days. (B) Atrial flutter. The atria begin a very rapid, perfectly regular "flapping" movement, beating at rates of 200 to 300 beats/min.

192 Figure 4. 20 (a) Atrial fibrillationFigure (a) Atrial fibrillation. The atria stop their regular beat and begin a feeble, uncoordinated twitching. Concomitantly, low-amplitude, irregular waves appear in the ECG, as shown. This type of recording can be clearly distinguished from the very regular ECG waveform containing atrial flutter. (b) Ventricular fibrillation. Mechanically the ventricles twitch in a feeble, uncoordinated fashion with no blood being pumped from the heart. The ECG is likewise very uncoordinated, as shown

193 Alteration of Potential Waveforms in IschemiaFigure (a) Action potentials recorded from normal (solid lines) and ischemic (dashed lines) myocardium in a dog. Control is before coronary occlusion. (b) During the control period prior to coronary occlusion, there is no ECG S-T segment shift; after ischemia, there is such a shift.

194 Electroencephalogram (EEG)EEG is a superposition of the volume-conductor fields produced by a variety of active neuronal current generators. The three type of electrodes to make the measurements are scalp, cortical, and depth. Topics in this section Gross anatomy and function of the brain Ultrastructure of the cerebral cortex The potential fields of single neuron Typical clinical EEG waveform Abnormal EEG waveform Superior Cerebrum Posterior Midbrain Cerebellum Caudal Inferior (a) Diencephalon Ventral Anterior Medulla oblongata Pons Dorsal The three main parts of the brain: Cerebrum Conscious functions Brainstem primitive functions such as controlling heart beat Integration center for motor reflexes Thalamus is integration center for sensory system Cerebellum (balance and voluntary muscle movement)

195 Anatomical relationship of brainstem structures (medulla oblongata, pons, midbrain, and diencephalons) to the cerebrum and cerebellum. General anatomic directions of orientation in the nervous system are superimposed on the diagram. Here the terms rostral (toward heard), caudal (toward tail), dorsal (back), and ventral (front) are associated with the brainstem; remaining terms are associated with the cerebrum. The terms medial and lateral imply nearness and remoteness respectively, to or from the central midline axis of the brain. (b) A simplified diagram of the CNS showing a typical general sense pathway from the periphery (neuron 1) to the brain (neuron 3). Note that the axon of the secondary neuron (2) in the pathway decussates (crosses) to the opposite side of the cord. Superior Diencephalon Cerebrum Posterior Anterior Midbrain Dorsal Pons Ventral Cerebellum Medulla oblongata Caudal Inferior (a) (b) Third ventricle 3 2 1 Cerebral hemisphere Peripheral nerve Thalamus Fourth ventricle Ascending spinothalamic tract Spinal cord Lateral ventricle Thalamocortical radiations

196 The cerebrum, showing the four lobes (frontal, parietal, temporal, and occipital), the lateral and longitudinal fissures, and the central sulcus. The cortex receives sensory information from skin, eyes, ears, and other receptors. This information is compared with previous experience and produces movements in response to these stimuli. SER: somatosensory evoked response AER: auditory evoked response VER: visual evoked response

197 The outer layer (1.5 – 4.0 mm) of the cerebrum is called cerebral cortex and consist of a dense collection of nerve cells that appear gray in color (gray matter). The deeper layer consists of axons (or white matter) and collection of cell body.

198 Neuron Cell in the CortexExcitatory synaptic input Lines of current flow +  Apical dendritic tree Basilar dendrites Axon Cell body (soma) EEG wave activity Two type of cells in the cortex Pyramidal cell Nonpyramidal cell - small cell body - Dendrites spring in all direction - Axons most of the times don’t leave the cortex Electrogenesis of cortical field potentials for a net excitatory input to the apical dendritic tree of a typical pyramidal cell. For the case of a net inhibitory input, polarity is reversed and the apical region becomes a source (+). Current flow to and from active fluctuating synaptic knobs on the dendrites produces wave-like activity.

199 Bioelectric Potential From the BrainConducted action potentials in axons contribute little to surface cortical records, because they usually occur asynchronously in time and at different spatial directions. Pyramid cells of the cerebral cortex are oriented vertically, with their long apical dendrites running parallel to one another. So, the surface records obtained signal principally the net effect of local postsynaptic potentials of cortical cells. Nonpyramidal cells in the neocortex are unlikely to contribute substantially to surface records because their dendritic trees are radially arranged around their cells, so the current sum to zero when viewed by electrode at a distance. When the sum of dendritic activity is negative relative to the cell, the cell is depolarized and quite excitable. When it is positive, the cell is hyperpolarized and less excitable.

200 Bioelectric Potential From the BrainWave group of the normal cortex -Alpha wave - 8 to 13 Hz, V, - Recorded mainly at the occipital region disappear when subject is sleep, change when subject change focus, see Fig. 4.27b -Beta wave (I and II) - 14 to 30Hz, during mental activity f=50Hz, beta I disappear during brain activity while beta II intensified. Recorded mainly at the parietal and frontal regions -Theta wave 4 to 7 Hz, appear during emotional stress such as disappointment and frustration Recorded at the parietal and temporal regions

201 Bioelectric Potential From the Brain-Delta wave Below 3.5 Hz, occur in deep sleep, occur independent of activity Occur solely within the cortex, independent of activities in lower regions of the brain. Synchronization is the underline process that bring a group of neurons into unified action. Synaptic interconnection and extracellular field interaction cause Synchronization. - Although various regions of the cortex capable of exhibiting rhythmic activity they require trigger inputs to excite rhythmicity. The reticular activation system (RAS) provide this pacemaker function.

202 EEG Waves Fig 4.27 (a) Different types of normal EEG waves. (b) Replacement of alpha rhythm by an asynchronous discharge when patient opens eyes. (c) Representative abnormal EEG waveforms in different types of epilepsy.

203 International Federation 10-20 SystemType of electrode connections 1- Between each member of a pair (bipolar) 2- Between one monopolar lead and a distant reference 3- Between one monopolar lead and the average of all.

204 EEG Waves During Sleep The electroencephalographic changes that occur as a human subject goes to sleep The calibration marks on the right represent 50 V.

205 The Abnormal EEG Two type of epilepsyEEG is used to diagnose different type of epilepsy and in the location of the focus in the brain causing the epilepsy. Causes of epilepsy could be intrinsic hyperexcitability of the neurons that make up the reticular activation system (RAS) or by abnormality of the local neural pathways of this system. Two type of epilepsy 1- Generalized epilepsy a- Grand mal b- petit mal (myoclonic form and absence form) 2- Partial epilepsy a- Jacksonian epilepsy b- Psychomotor seizure (amnesia, abnormal rage, sudden anxiety or fear, incoherent speech)

206 Chapter 5-Webster Biopotential Electrodes

207 Outline Basic mechanism of transduction processElectrical characteristics of biopotential electrodes Different type of biopotential electrodes Electrodes used for ECG, EEG, MEG, and intracellular electrodes

208 Biopotential Electrodes- A transducer that convert the body ionic current in the body into the traditional electronic current flowing in the electrode. - Able to conduct small current across the interface between the body and the electronic measuring circuit.

209 Electrode-Electrolyte InterfaceOxidation reaction causes atom to lose electron Reduction reaction causes atom to gain electron Oxidation is dominant when the current flow is from electrode to electrolyte, and reduction dominate when the current flow is in the opposite. Oxidation Reduction anion cation Current flow Current flow

210 Half-Cell Potential Half-Cell potential is determined byMetal involved Concentration of its ion in solution Temperature And other second order factor Certain mechanism separate charges at the metal-electrolyte interface results in one type of charge is dominant on the surface of the metal and the opposite charge is concentrated at the immediately adjacent electrolyte.

211 Half-Cell Potential Standard Hydrogen electrodeHalf-cell potential for common electrode materials at 25 oC Standard Hydrogen electrode Electrochemists have adopted the Half-Cell potential for hydrogen electrode to be zero. Half-Cell potential for any metal electrode is measured with respect to the hydrogen electrode.

212 Oxidation Reduction -

213 Polarization Half cell potential is altered when there is current flowing in the electrode due to electrode polarization. Overpotential is the difference between the observed half-cell potential with current flow and the equilibrium zero-current half-cell potential. Mechanism Contributed to overpotential Ohmic overpotential: voltage drop along the path of the current, and current changes resistance of electrolyte and thus, a voltage drop does not follow ohm’s law. Concentration overpotential: Current changes the distribution of ions at the electrode-electrolyte interface - Activation overpotential: current changes the rate of oxidation and reduction. Since the activation energy barriers for oxidation and reduction are different, the net activation energy depends on the direction of current and this difference appear as voltage. Note: Polarization and impedance of the electrode are two of the most important electrode properties to consider.

214 Half Cell Potential and Nernst EquationWhen two ionic solutions of different concentration are separated by semipermeable membrane, an electric potential exists across the membrane. a1 and a2 are the activity of the ions on each side of the membrane. Ionic activity is the availability of an ionic species in solution to enter into a reaction. Note: ionic activity most of the time equal the concentration of the ion If the activity is not unity (activity does not equal concentration) then the cell potential is For the general oxidation-reduction reaction, the Nernst equation for half cell potential is

215 Example 5.1 An electrode consisting of a piece of Zn with an attached wire and another electrode consisting of a piece of Ag coated with a layer of AgCl and an attached wire are placed in a 1 M ZnCl2 solution (activities of Zn2+ and Cl- are approximately unity) to form an electrochemical cell that is maintained at a temperature of 25 oC. What chemical reactions might you expect to see at these electrodes? If a very high input impedance voltmeter were connected between these electrodes, what would it read? If the lead wires from the electrodes were shorted together, would a current flow? How would this affect the reactions at the electrodes? How would you expect the voltage of the cell immediately following removal of the short circuit?

216 Polarizable and Nonpolarizable ElectrodesPerfectly Polarizable Electrodes Electrodes in which no actual charge crosses the electrode-electrolyte interface when a current is applied. The current across the interface is a displacement current and the electrode behaves like a capacitor. Overpotential is due concentration. Example : Platinum electrode Perfectly Non-Polarizable Electrode Electrodes in which current passes freely across the electrode- electrolyte interface, requiring no energy to make the transition. These electrodes see no overpotentials. Example: Ag/AgCl Electrode Example: Ag-AgCl is used in recording while Pt is used in stimulation

217 The Silver/Silver Chloride ElectrodeApproach the characteristic of a perfectly nonpolarizable electrode Advantage of Ag/AgCl is that it is stable in liquid that has large quantity of Cl- such as the biological fluid. 1.5 v Ag/AgCl exhibits less electric noise than the equivalent metallic Ag electrode. Ag AgCl Read in text other process to make electrode such as sintering process.

218 The Silver/Silver Chloride ElectrodeSilver chloride’s rate of precipitation and of returning to solution is a constant Ks know as the solubility product. For biological fluid where Cl- ion is relatively high

219 Example 5.2 An AgCl surface is grown on an Ag electrode by the electrolytic process described in the previous paragraph. The current passing through the cell is measured and recorded during the growth of the AgCl layer and is found to be represented by the equation I = 100e-t/10s mA If the reaction is allowed to run for a long period of time, so that the current at the end of this period is essentially zero; how much charge is removed from the battery during this reaction? How many grams of AgCl are deposited on the Ag electrode’s surface by this reaction?

220 Electrode Behavior and Circuit Modelsmetal + Electrolyte - Rd and Cd make up the impedance associated with electrode-electrolyte interface and polarization effects. Rs is associated with interface effects and due to resistance in the electrolyte.

221 Characteristic of ElectrodeThe characteristic of an electrode is Sensitive to current density Waveform and frequency dependent

222 Electrode Behavior and Circuit Modelsmetal + - Electrolyte 1 cm2 nickel-and carbon-loaded silicone rubber electrode

223 Electrode Behavior and Circuit ModelsTo model an electrode (test electrode), it was placed in a physiological saline bath in the laboratory, along with an Ag/AgCl electrode (reference electrode) having a much grater surface area and a known half-cell potential of V. The dc voltage between the two electrodes is measured with a very-high-impedance voltmeter and found to be V with the test electrode negative. The magnitude of the impedance between the two electrodes is measured as a function of frequency at very low currents; it is shown below. From these data, determine a circuit model for the electrode.

224 Electrode Behavior and Circuit Models0.572 - + 0.233 V Ex Test Electrode Reference Electrode

225 The Electrode-Skin Interface and Motion ArtifactTransparent electrolyte gel containing Cl- is used to maintain good contact between the electrode and the skin.

226 The Electrode-Skin InterfaceSweat glands and ducts Electrode Epidermis Dermis and subcutaneous layer Ru Re Ese Ehe Rs Rd Cd EP RP CP Ce Gel For 1 cm2, skin impedance reduces from approximately 200K at 1Hz to 200 at 1MHz. 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 left-hand diagram.

227 Motion Artifact When polarizable electrode is in contact with an electrolyte, a double layer of charge forms at the interface. Movement of the electrode will disturb the distribution of the charge and results in a momentary change in the half cell potential until equilibrium is reached again. Motion artifact is less minimum for nonpolarizable electrodes. Signal due to motion has low frequency so it can be filtered out when measuring a biological signal of high frequency component such as EMG or axon action potential. However, for ECG, EEG and EOG whose frequencies are low it is recommended to use nonpolarizable electrode to avoid signals due to motion artifact.

228 Body-Surface Recording Electrode Metal-Plate ElectrodesBody-surface biopotential electrodes (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 electrocardiograph monitoring apparatus.

229 Body-Surface Recording Electrode Suction ElectrodesA metallic suction electrode is often used as a precordial electrode on clinical electrocardiographs. No need for strap or adhesive and can be used frequently. Higher source impedance since the contact area is small

230 Body-Surface Recording Electrode Floating ElectrodesDouble-sided Adhesive-tape ring Insulating package Metal disk Electrolyte gel in recess (a) (b) (c) Snap coated with Ag-AgCl External snap Plastic cup Tack Plastic disk Foam pad Capillary loops Dead cellular material Germinating layer Gel-coated sponge The recess in this electrode is formed from an open foam disk, saturated with electrolyte gel and placed over the metal electrode. Minimize motion artifact

231 Body-Surface Recording Electrode Flexible ElectrodesFlexible body-surface electrodes (a) Carbon-filled silicone rubber electrode. (b) Flexible thin-film neonatal electrode. (c) Cross-sectional view of the thin-film electrode in (b). Used for newborn infants. Compatible with X-ray Electrolyte hydrogel material is used to hold electrodes to the skin.

232 Internal Electrodes No electrolyte-skin interfaceNo electrolyte gel is required Needle and wire electrodes for percutaneous measurement of biopotentials (a) Insulated needle electrode. (b) Coaxial needle electrode. (c) Bipolar coaxial electrode. (d) Fine-wire electrode connected to hypodermic needle, before being inserted. (e) Cross-sectional view of skin and muscle, showing coiled fine-wire electrode in place. For EMG Recording

233 Internal Electrodes Electrodes for detecting fetal electrocardiogram during labor, by means of intracutaneous needles (a) Suction electrode. (b) Cross-sectional view of suction electrode in place, showing penetration of probe through epidermis. (c) Helical electrode, which is attached to fetal skin by corkscrew type action.

234 Electrode Arrays (c) Tines Base Exposed tip Contacts Insulated leads (b) Ag/AgCl electrodes (a) (a) One-dimensional plunge electrode array 10mm long, 0.5mm wide, and 125m thick, used to measure potential distribution in the beating myocardium (b) Two-dimensional array, used to map epicardial potential and (c) Three-dimensional array, each tine is 1,5 mm

235 Microelectrodes Used in studying the electrophysiology of excitable cells by measure potential differences across the cell membrane. Electrode need to be small and strong to penetrate the cell membrane without damaging the cell. Tip diameters = 0.05 to 10 m Metal rod Tissue fluid Membrane potential N C B N = Nucleus C = Cytoplasm A Reference electrode Insulation Cd Cell membrane + 

236 The structure of a metal microelectrode for intracellular recordings.Microelectrodes The structure of a metal microelectrode for intracellular recordings. Figure 5.18 Structures of two supported metal microelectrodes (a) Metal-filled glass micropipet. (b) Glass micropipet or probe, coated with metal film.

237 Microelectrodes A glass micropipet electrode filled with an electrolytic solution (a) Section of fine-bore glass capillary. (b) Capillary narrowed through heating and stretching. (c) Final structure of glass-pipet microelectrode.

238 Electrodes For Electric Stimulation of TissuePolarization potential  i t Ohmic (b) Current and voltage waveforms seen with electrodes used for electric stimulation (a) Constant-current stimulation. (b) Constant-voltage stimulation.