GBM8320 Dispositifs Médicaux Intelligents

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1 GBM8320 Dispositifs Médicaux Intelligents Biopotential amplifiers Part 1 Mohamad Sawan et al. Laboratoire de neurotechnologies Polystim mohamad.sawan@polymtl.ca M February 2011 Biopotential amplifiers: Course outline Biopotentials measurement Principle, requirements, and metrics Types of biopotential External Interference and intrinsic noises Sources and models Instrumentation amplifiers Discrete and integrated Advanced instrumentation amplifiers Integrated biopotential amplifiers Examples, and practical implementations GBM Dispositifs Médicaux Intelligents 2 Principle of biopotential measurement Function of a biopotential amplifier: to take a weak electric biological signal, increase its amplitude, and extract it from ambient noise so it can be further processed, recorded, or displayed. Bioamplifiers are also used to isolate the load from the source. In that case, the amplifier may provides only a current gain to drive the load, leaving the voltage amplitude of the input signal unchanged (Example: a voltage follower). Most biopotential amplifiers are voltage amplifiers, but current or power can also be addressed. Design considerations include proper amplification and bandwidth, high input impedance, low intrinsic noise, interference rejection, stability against temperature and voltage fluctuations, and safety. GBM Dispositifs Médicaux Intelligents 3

2 Principle of biopotential measurement Block diagram of a biopotential measurement system Biopotentials exhibit small amplitudes (1 µv to 10 mv) and low frequencies (0.1 Hz to 10 khz). Biopotential measurements are corrupted by environmental and biological sources of interference. A first rank biopotential amplifier must implement a suitable interface. Dominates the SNR of the whole recording channel electrode Gain stage GBM Dispositifs Médicaux Intelligents 4 Principle of biopotential measurement Basic requirements (What is a suitable interface?) High input impedance: Z in > 10 MΩ for loading the source/electrode minimally; Bandwidth: Must let the signal spectrum unchanged and optimize the SNR; Amplification: A high gain is needed to boost the signal so it becomes suitable for display, and subsequent processing modules; Low intrinsic noise: Must provide a suitable SNR (Its input referred-noise must be a few times smaller than the input signal); High noise rejection: Must reject ambient noise and interference; Protection input circuits : Voltage or leaking currents in the input could affect the signal, damage the circuit or arm the patient s body; Output impedance: Low or high. It provides source impedance adaptation to suit the load; Calibration: Accurate and exact measurement of amplitude values are required for physicians. GBM Dispositifs Médicaux Intelligents 5 Principle of biopotential measurement Important bioamplifier metrics and glossary Bandwidth (in Hz), gain, attenuation (in db) Input referred noise (in V/ Hz or Vrms): V ni2 = V no2 / Gain 2 Signal-to-noise ratio (SNR in db): SNR = 10 log (V s2 /V n2 ) Noise rejection - Common mode rejection ratio (CMRR in db) Dynamic range (DR) and Linear range (in db) measured for 1% distortion DR = 10 log (V smax2 /V smin2 ) Signal-to-noise and distortion ratio (SNDR in db) Total harmonic distortion (THD in db or percentage) and Nth-order harmonic distortion terms (ex.: HD3, HD5) Inter-modulation distortion (IMD in db) and Nth-order inter-modulation terms (ex.: IMD2, IMD3, IMD5) Figure of merit: Give an indication of how well the design trade-offs are resolved in an amplifier. Ex.: Noise efficiency factor (NEF), and other FOM GBM Dispositifs Médicaux Intelligents 6

3 Common biopotential signals Action potential (AP - intra or extracellular): Measurement of the electrical potential resulting from the cell membrane depolarization; Local field potential (LFP): The sum of all dendritic synaptic activity within a volume of tissue measured with a low impedance microelectrode; Electroneurogram (ENG): Neural activity conveyed by nerves from or to innervated organs (Mixture of APs); Electroencephalogram (EEG): Measured on the scalp. Low frequency waves; Electrocardiogram (ECG): Heart activity measured on the chest; Electromyogram (EMG): Muscle activity measured on the skin, or in muscles; Electrocorticogram (ECoG): Measured with electrodes placed directly on the surface of the brain (under the skull). ECoG is currently considered to be the gold standard for defining epileptogenic zones in clinical practice; Electrooculogram (EOG): Electric potentials generated as a result of movement of the eyeballs measured on or off the eye. Electroretinography (ERN): measures the individual electrical responses of various cell types in the retina, including photoreceptors, inner retinal cells, & ganglion cells. GBM Dispositifs Médicaux Intelligents 7 Characteristics of biopotentials Voltage and frequency ranges of some biopotential signals (From electrodes) AP Intracellular AP LFP ( Hz) Extracellular AP ENG (1 µv 20 µv) GBM Dispositifs Médicaux Intelligents 8 Characteristics of biopotentials Characteristics of some biopotentials Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, GBM Dispositifs Médicaux Intelligents 9

4 Characteristics of biopotentials Characteristics of some biopotentials (cont d) Type of neural signals Distinguishing features Amplifier design consideration Additional features desired Intracellular APs Extracellular APs (spikes) 10 mv 80 mv, 100 Hz 10 khz 10 µv 100 µv, 100 Hz 10 khz Gain > 40 db Electrode DC potential rejection, Gain > 60 db Measured with a glass needle microelectrode Measured with thin microelectrodes Local field potentials (LFPs) 0.1 Hz 100 Hz, 1 mv 10 mv Gain > 40 db Sum of dentritic current measured with a large microelectrode tip ENG: mixture of APs measured on nerve bundles 100 Hz 10 khz, 1 µv 10 µv Gain > 80 db, Very lownoise and extremely high CMRR Measured on the nerve with a cuff electrode GBM Dispositifs Médicaux Intelligents 10 Characteristics of common biopotentials Sample biopotential waveforms (a) ECG, normal sinus rhythm; (b) EEG, normal patient with open eyes; (c) EMG, flexion of biceps muscles; (d) EOG, movement of eyes from left to right. Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, GBM Dispositifs Médicaux Intelligents 11 Characteristics of common biopotentials (e) Local field potentials (f) ENG Harrison et al., Local field potential measurement EMBS, Wenzel et al., Detecting the onset of hyper-reflexive bladder.., EMBS, GBM Dispositifs Médicaux Intelligents 12

5 Characteristics of common biopotentials (g) Intracellular APs (h) Extracellular APs (spikes) Gosselin et al., "A Low-Power Integrated Bioamplifier.," TBioCAS, v1, GBM Dispositifs Médicaux Intelligents 13 Pre-processing of extracellular AP recordings High-density recording of unit activity in the somatosensory cortex of the rat (a) Placement of an eight-shank silicon probe in layer 5 (8 sites per probe); (a) A short epoch of raw recording, illustrating both field and unit activity (1 5 khz); (c) Two-dimensional views of unit clusters (out of 28 possible views from an eight-site probe) from one shank. Buzsáki, Large-scale recording of neuronal ensembles, N. Neuroscience, V7, GBM Dispositifs Médicaux Intelligents 14 Analysis of extracellular AP recordings Joint peristimulus time histogram (JPSTH) Parametric fitting (assume a probability model) Crosscorrelogram Crosscoherence function (frequency domain) Brown et al. Multiple neural spike train data analysis, Nat Neurosci, v7, Nicolelis et al., Reconstructing the engram: simultaneous, Neuron, v18, GBM Dispositifs Médicaux Intelligents 15

6 Recording APs for use in prosthetic devices Population encoding of movements Cells vary firing rates with direction of movement. Almost all cells show some modulation with each direction Georgopoulos et al., J. Neurosci, Population vectors: Vector contributions of each of the 241 directionally tuned cells Length of vector is proportional to the % change in firing rate from the mean firing rate. GBM Dispositifs Médicaux Intelligents 16 Instrumentation amplifiers Differential measurements + A d, A cm _ v o Ideally vid vid vo = A( v2 v1) = A( vicm + ( vicm )) = Av 2 2 Id However A d v CMRR = 20log o = AcmvIcm + Ad vid Acm GBM Dispositifs Médicaux Intelligents 17 Instrumentation amplifiers Three-opamps amplifier The right side shows a oneop-amp differential amplifier, but it has low input impedance; The left side provides high input impedance and additional gain; We have ( v3 v4) ( v1 v i = and i = 2) 2R2 + R1 R1 Thus, the diff gain (A1) of the input v 3 v4 2R2 + R1 stage is = v v R1 1 2 The diff gain of the second stage is The total diff gain is v o R4 = v v R v o R4 2R2 + R1 = v1 v2 R3 R1 GBM Dispositifs Médicaux Intelligents 18

7 Instrumentation amplifiers Three-opamps amplifier A cm ideally unity in the first stage and = 0 in the differential amp; However, if R3 R3 and R4 R4, the output of the instrumentation amplifier is R4 R3' + R4' R4 v o = v3 v4 R3+ R4 R3' R3 or, R4 R3' + R4' R4 vo = A1 v1 v2 R3 + R4 R3' R3 R4 R3' + R4' R4 R4 R3' + R4' R4 = A1 vicm + vid + R3 + R4 R3' R3 R3 + R4 R3' R3 v = A v + A v o cm Icm d Id A cm A d GBM Dispositifs Médicaux Intelligents 19 Instrumentation amplifiers Tunable instrumentation amplifier with a bandpass characteristic The gain of the first stage (amplifiers A1 and A2) is 1+2 R2/R1, the second stage (amplifier A3) is - R4/R3, and the third stage (amplifier A4) is 1+R7/R6. The lower corner frequency is 1/(2πR5C1) and the upper corner frequency is 1/(2πR7C2). The variable resistor R4 is adjusted to maximize the CMRR. E1 and E2 are the recording electrode terminals while E3 is the reference or the ground electrode terminal. Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, GBM Dispositifs Médicaux Intelligents 20 Instrumentation amplifiers Monolithic low-power precision instrumentation amplifier LOW INPUT-REFERRED NOISE: 10 nv/sqrt(hz) at 1 khz HIGH CMR: 110dB min LOW OFFSET VOLTAGE: 50 µv max LOW DRIFT: 0.5µV/ C max LOW INPUT BIAS CURRENT: 5nA max INPUTS PROTECTED TO ±40V WIDE SUPPLY RANGE: ±1.35 to ±18V LOW QUIESCENT CURRENT: 350mA The INA118 is a low power, general purpose instrumentation amplifier offering excellent accuracy. Its versatile 3-op amp design and small size make it ideal for a wide range of applications. The INA118 is laser trimmed for very low offset voltage (50 µv), drift (0.5 µv/ C) and high common-mode rejection (110dB at G = 1000). GBM Dispositifs Médicaux Intelligents 21

8 Instrumentation amplifiers High-input impedance AC coupled instrumentation amplifier A highpass cutoff frequency is obtained by connecting a Miller integrator from the amplifier output to its reference terminal. GBM Dispositifs Médicaux Intelligents 22 Electrical and biological interference Examples: External interference in ECG recordings (a) Baseline changes and motion artifacts; (b) Muscle signal interference; (c) Electromagneti c interference (60 Hz power line and RF); Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, GBM Dispositifs Médicaux Intelligents 23 Electrical and biological interference Example : External interference in ECG recordings (d) Respiration Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, GBM Dispositifs Médicaux Intelligents 24

9 Electrical interference and noise Electric-field pickup in an electrocardiograph C1-C3 are coupling capacitances; This causes displacement currents to flow through skinelectrode impedances on its way to ground (Z 1, Z 2 > Z G ) v v = i A B d1z1 id 2Z 2 v v = i ( Z ) 2 A i i d1 d 2 B d1 1 Z GBM Dispositifs Médicaux Intelligents 25 Electrical interference Example Typically, i d 6 na for a 9-m cable, and skin-electrode impedances may differ by as much as 20 kω. Hence, we can calculate the resulting differential voltage pick-up at the amplifier inputs: v v = i ( Z ) 2 A B d1 1 Z v A v B = (6 na)(20 kω) = 120 µv This interference can be minimized by shielding the leads and grounding each at the electrocardiograph and/or lowering the skin-electrode contact impedances. GBM Dispositifs Médicaux Intelligents 26 Electrical interference Common-mode voltage everywhere on the body A displacement current flows from the power line through the body and ground impedance This creates a common-mode voltage everywhere on the body. Z in is not only resistive but, as a result of AC couplings or RF bypass capacitors at the amplifier input, has a reactive component as well. v = i cm db Z G GBM Dispositifs Médicaux Intelligents 27

10 Electrical interference Example Substituting with typical values for the common mode voltage yields v cm = i db Z G = (0.2 µa)(50 kω) = 10 mv v cm turns in a differential voltage because the input impedance of the amplifier is finite and Z 1 Z 2 v v A B = v cm Zin Zin Zin + Z Zin + 1 Z 2 Z 2 Z1 v = A vb vcm Zin v A v B = ( 10 mv)(20 kω/5 MΩ) = 40 µ V GBM Dispositifs Médicaux Intelligents 28 Electrical interference reduction Driven-right-leg circuit for minimizing common- mode interference The circuit derives the commonmode voltage from a pair of averaging resistors connected to v 3 and v 4 in the instrumentation amplifier; This sensed voltage is inverted, amplified, and fed back to the body. This negative feedback drives v cm to a low value. The right leg is not grounded but is connected to the output of the auxiliary opamp. R o must be chosen large in order to limit the current at safe values. GBM Dispositifs Médicaux Intelligents 29 Electrical interference reduction Equivalent Driven-rightleg circuit R RL represents the resistance of the right-leg electrode; Summing the current at the negative input, we get 2vcm vo R + a R f 2Rf = Ra = 0 v o v cm v cm = RRLid + vo RRLid vcm = + 2R / R 1 f a (1) (2) (3) (4) GBM Dispositifs Médicaux Intelligents 30

11 Electrical interference reduction Example Determine v cm on the patient when the driven-right-leg circuit is used. Choose appropriate values for the resistances in the circuit so that v cm is minimal. What is v cm for a displacement current of i d = 0.2 µa. According to Eq. (4), the effective resistance between the right leg and ground is R RL /( 1+ 2Rf / Ra ) R o should be large to limit current. Values as high as 5 MΩ are used. The voltage v cm is made small by providing a low-resistance path to ground (by making R RL small). Thus, R f must be large and R a small. R f can equal R o, and R a typically equals 25 kω. For an electrode with resistance R RL = 100 kω, the effective resistance between the right leg and ground would then be 100 kω /( MΩ / 25 kω) = 249 Ω For i d = 0.2 µa, the v cm is v cm = 249 Ω 0.2 µ A = 50 µ V, compared to 10 mv without driven-right-leg circuit. GBM Dispositifs Médicaux Intelligents 31