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GBM8320Dispositifs Médicaux Intelligents

Biopotential amplifiers – Part 1Mohamad Sawan et al.

Laboratoire de neurotechnologies Polystim

http://www.cours.polymtl.ca/gbm8320/[email protected]

M5418

4 February 2011

GBM8320 - Dispositifs Médicaux Intelligents 2

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


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.


Principle of biopotential measurementBlock 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

Gain stageelectrode


Principle of biopotential measurementBasic requirements (What is a suitable interface?)• High input impedance: Zin > 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.


Principle of biopotential measurementImportant bioamplifier metrics and glossary• Bandwidth (in Hz), gain, attenuation (in dB)• Input referred noise (in V/√Hz or Vrms): Vni

2 = Vno2 / Gain2

• Signal-to-noise ratio (SNR in dB): SNR = 10 log (Vs2/Vn

2)• Noise rejection - Common mode rejection ratio (CMRR in dB)• Dynamic range (DR) and Linear range (in dB) – measured for 1% distortion

DR = 10 log (Vsmax2/Vsmin

2)• 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


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.


Characteristics of biopotentials

© Webster, Medical instrumentation: application and design. 3rd ed. Wiley, 1998.

Voltage and frequency ranges of some biopotential signals

AP

Intracellular AP

Extracellular AP

ENG (1 µV – 20 µV)

(From electrodes)

LFP (0.1–10 Hz)


Characteristics of biopotentialsCharacteristics of some biopotentials

Webster, The Measurement, Instrumentation and Sensors Handbook, CRC, 1998.


Characteristics of biopotentialsCharacteristics of some biopotentials (cont’d)

Type of neural signals Distinguishing features

Amplifier design consideration

Additional features desired

Intracellular APs 10 mV – 80 mV, 100 Hz – 10 kHz

Gain > 40 dB Measured with a glass needle microelectrode

Extracellular APs(spikes)

10 µV – 100 µV, 100 Hz – 10 kHz

Electrode DC potential rejection, Gain > 60 dB

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 APsmeasured on nerve bundles

100 Hz – 10 kHz, 1 µV – 10 µV

Gain > 80 dB, Very low-noise and extremely high CMRR

Measured on the nerve with a cuff electrode


Characteristics of common biopotentialsSample 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.



Characteristics of common biopotentials

(e) Local field potentials

(f) ENG

Wenzel et al., “Detecting the onset of hyper-reflexive bladder …..”, EMBS, 2004.Harrison et al., “Local field potential measurement …” EMBS, 2004.


Characteristics of common biopotentials

(g) Intracellular APs (h) Extracellular APs (spikes)

Gosselin et al., "A Low-Power Integrated Bioamplifier ….," TBioCAS, v1, 2007.http://spikoscope.sourceforge.net/Spikoscope/Extracellular.html


Pre-processing of extracellular AP recordings

Buzsáki, “Large-scale recording of neuronal ensembles,” N. Neuroscience, V7, 2004.

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.


Analysis of extracellular AP recordings

• Brown et al. “Multiple neural spike train data analysis…,” Nat Neurosci, v7, 2004.• Nicolelis et al., “Reconstructing the engram: simultaneous, …” Neuron, v18, 1997.

Cross-correlogram

Cross-coherence

function(frequency domain)

Joint peri-stimulus time

histogram (JPSTH)

Parametric fitting

(assume a probability

model)


Recording APs for use in prosthetic devicesPopulation encoding of movements

Georgopoulos et al., J. Neurosci, 1982.

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.

Cells vary firing rates with direction of movement. Almost all cells show some modulation with each direction


Instrumentation amplifiersDifferential measurements

• Ideally

• However

( ) Idv

Icmv

Icmo AvvvAvvAv IdId =−−+=−= )()( 2212

=

cm

d

AACMRR log20IddIcmcmo vAvAv +=

vo

+

_Ad, Acm


Instrumentation amplifiersThree-opamps amplifier

•The right side shows a one-op-amp differential amplifier, but it has low input impedance;•The left side provides high input impedance and additional gain;•We have

•Thus, the diff gain (A1) of the input stage is

122)( 43

RRvvi+−

=1

)( 21

Rvvi −

=

1122

21

43

RRR

vvvv +

=−−

34

43 RR

vvvo −=−

+

−=− 1

12234

21 RRR

RR

vvvo

and • The diff gain of the second stage is

• The total diff gain is

‘

‘



Three-opamps amplifier

• Acm 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

or,

Instrumentation amplifiers

34

'3'4'3

434

43 RRv

RRR

RRRvvo −

+

+=

+

+

++

−

+

+⋅=

−

+

+⋅=

34

'3'4'3

434

34

'3'4'3

4341

34

'3'4'3

4341 21

RR

RRR

RRRv

RR

RRR

RRRvA

RRv

RRR

RRRvAv

IdIcm

o

Acm AdIddIcmcmo vAvAv +=


Instrumentation amplifiersTunable 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.


Instrumentation amplifiersMonolithic 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).


Instrumentation amplifiersHigh-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.


Electrical and biological interferenceExamples: External interference in ECG recordings


(a) Baseline changes and motion artifacts;

(b) Muscle signal interference;

(c) Electromagnetic interference (60 Hz power line and RF);


Electrical and biological interferenceExample : External interference in ECG recordings


(d) Respiration


Electrical interference and noiseElectric-field pickup in an electrocardiograph

•C1-C3 are coupling capacitances;

•This causes displacement currents to flow through skin-electrode impedances on its way to ground (Z1, Z2 > ZG)

2211 ZiZivv ddBA −=−

)( 211 ZZivv dBA −=−

21 dd ii ≅



Electrical interferenceExample

Typically, id ≅ 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:

This interference can be minimized by shielding the leads and grounding each at the electrocardiograph and/or lowering the skin-electrode contact impedances.

vA − vB = (6 nA)(20 kΩ) = 120 µV

)( 211 ZZivv dBA −=−


Electrical interferenceCommon-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. • Zin 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.

Gdbcm Ziv =



Electrical interferenceExample

• Substituting with typical values for the common mode voltage yields

• vcm turns in a differential voltage because the input impedance of the amplifier is finite and Z1 ≠ Z2

vcm = idbZG = (0.2 µA)(50 kΩ) = 10 mV

+

−+

=−21 ZZ

ZZZ

Zvvvin

in

in

incmBA

−=−

incmBA Z

ZZvvv 12

V 40)M /5k 20)(mV 10( µ=ΩΩ=− BA vv



Electrical interference reduction


Driven-right-leg circuit for minimizing common- mode interference

•The circuit derives the common-mode voltage from a pair of averaging resistors connected to v3 and v4 in the instrumentation amplifier;

•This sensed voltage is inverted, amplified, and fed back to the body.

•This negative feedback drives vcmto a low value.

• The right leg is not grounded but is connected to the output of the auxiliary opamp.

• Ro must be chosen large in order to limit the current at safe values.


Electrical interference reductionEquivalent Driven-right-

leg circuit• RRL represents the resistance of the right-leg electrode;• Summing the current at the negative input, we get

0f

2 =+ Rv

Rv o

a

cm

cmRR

o vva

f2−=

odRLcm viRv +=

a

dRLcm RR

iRv/21 f+

=

(1)

(2)

(3)

(4)



Electrical interference reductionExample

Determine vcm on the patient when the driven-right-leg circuit is used. Choose appropriate values for the resistances in the circuit so that vcm is minimal. What is vcm for a displacement current of id = 0.2 µA.

According to Eq. (4), the effective resistance between the right leg and ground is

Ro should be large to limit current. Values as high as 5 MΩ are used. The voltage vcm is made small by providing a low-resistance path to ground (by making RRL small). Thus, Rfmust be large and Ra small. Rf can equal Ro, and Ra typically equals 25 kΩ. For an electrode with resistance RRL = 100 kΩ, the effective resistance between the right leg and ground would then be

For id = 0.2 µA, the vcm is , compared to 10 mV without driven-right-leg circuit.

)/21/( f aRL RRR +

Ω=ΩΩ×+Ω 249)k 25/M 521/(k 100

V 50A 2.0 249 µµ =×Ω=cmv

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