bioimpedance - iirc · 2019. 3. 3. · bioimpedance eung je woo department of biomedical...
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Bioimpedance
Eung Je Woo
Department of Biomedical Engineering
Impedance Imaging Research Center (IIRC)
College of Medicine
Kyung Hee University
Korea
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Conductivity and Resistance
V
I
I
L
S
MobileIons
-+
e-
e-
V+_ V
I
I
-+
e-
e-
MobileIons
V+
_
𝐄 = −𝛻𝑢, 𝐅 = 𝑞𝐄 = 𝑚𝐚, 𝐯𝑑 = 𝜇𝐄
𝐼 = 𝑅𝑉, 𝑅 =𝑉
𝐼=
1
𝜎
𝐿
𝑆
𝐉 = 𝑐𝐯𝑑 = 𝑐𝜇𝐄 = 𝜎𝐄 = −𝜎𝛻𝑢
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- - - - - - - - -+Q
-Q
L
S
PolarizationImmobile Polar Molecules
Permittivity and Capacitance
e-
e-
e-
e- +Q
-Q
𝑞 𝑡 = 𝐶𝑣 𝑡 = 𝜀𝑆
𝐿𝑣 𝑡 , 𝑖 𝑡 =
𝑑𝑞(𝑡)
𝑑𝑡= 𝐶
𝑑𝑣(𝑡)
𝑑𝑡
𝑣 𝑡 = 𝑉 cos𝜔𝑡 , 𝑖 𝑡 = −𝑉𝜔𝐶 sin𝜔𝑡
𝑣(𝑡) = 𝑅𝑒 𝑉𝑒𝑗𝜔𝑡 , 𝑖 𝑡 = 𝑅𝑒 𝑉𝜔𝐶𝑒𝑗 𝜔𝑡+90°, 𝐙 =
𝐕
𝐈=
1
𝑗𝜔𝐶
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-Cl+Na
-Cl+Na
+Na -Cl
+ + + + + + +
+ + + + + + +
_ _ _ _ _ _ _
_ _ _ _ _ __
i(t)
+
v(t)
-
1 2
1 2
1 1R jX R R
j C j C Z
cos , sin
R jX Z
R Z X Z
Z
( ) sin and
( ) sin
m
m
i t I t
v t I Z t
i(t)
1
1
2
2
R
C
C
R
Cell Membrane
Extra-cellular Fluid
Intra-cellular Fluid
+
v(t)
-
Admittivity and Impedance (or Admittance)
, , ,j r r r
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Extra-cellularFluid
Intra-cellularFluid
CellularMembrane
Tissue Model (Macroscopic Apparent Conductivity)
-+
+
-
+
-
-
+ +
- -
+
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Tissue Conductivity (Tumor)
Haemmerich et al., Physiol. Meas., 2003.
Normal Tumor
Necrosis
Fibrosis
Liver Breast
Lobular Carcinoma Ductal Carcinoma
Normal
Normal tissue
Central part of tumor
Surowiec et al., IEEE Trans. Biomed. Eng., 1988.
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Tissue Conductivity (Lung Ventilation and Perfusion)300 million alveoli
Ventilation
Perfusion
Z : 10 mW to 40 W
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• Molecular composition of cells
• Shape and direction of cells
• Density and structure of cells
• Contents of extra-cellular matrix
• Concentration and mobility of ions
• Concentration and mobility of charge-carrying molecules
• Amounts of intra- and extra-cellular fluids
• Lung ventilation and perfusion
• Cardiac function and hemodynamics
• Sleep apnea
• Tumor
• Bleeding
• Gastric emptying
• Stoke
• Epilepsy
• Neural activity
• Temperature or ablation
Structure and Composition Function and Pathology
Tissue Conductivity
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Tissue Conductivity (1 Hz – 1 MHz)
Tissue Conductivity [S/m] Anisotropy
Lung 0.05 – 0.6 Local
Whole blood 0.7 Flow dependent
Bone 0.005 – 0.06 Strong
Muscle 0.05 – 0.6 Strong
Fat 0.02 – 0.05 Small
Liver 0.2 – 0.3 Unknown
Saline, 0.9% 2 None
Sea water 5 None
Low- and high-frequency current paths in biological tissue
Grimnes and Martinsen, 2008
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Body as a Passive Volume Conductor
Malmivuo and Plonsey, 1995
Conductivity Voltage
Injection Current
⋅ 𝜎 𝐫, 𝑡 𝑢 𝐫, 𝑡 = 0 in Ω
−𝜎 𝐫, 𝑡 𝑢 𝐫, 𝑡 ⋅ 𝐧 = 𝑔 on 𝜕Ω
Current Density
𝐉 𝐫, 𝑡 = −𝜎 𝐫, 𝑡 𝑢 𝐫, 𝑡
u
, r
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Homogeneous Conductivity (Toy Problem)
22
2
0
0
, 0z L z
uu
z
u V u
V
u z zL
z
Vz u z
L
- -J a
zS
VI z dxdy S
L
- J a
1 [ ]
VR
I
L
S W
V
0 z = 0
z = LS
J
V
0
I
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Geometrical Effect (Toy Problem)
Grimnes and Martinsen, 2008
2
2
0
10
, 0
ur
r r r
u r a V u r
0aVu r
r
0
2 r
aVr u r
r
- J a
2002Half sphere
2 2aV
I r d r a Vr
J r
0 1 [ ]
2
VR
I a W
V0
a
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Geometrical Effect (Toy Problem)
2
2
0
10
, 0
ur
r r r
u r a V u r b
0 1aV b
u rb a r
-
-
0
2 r
abVr u r
b a r
-
-J a
20 0
2Half sphere2 2
abV ab VI r d r
b a r b a
- - J r
0 1 1 1 [ ]
2 b
V
I aR
- W
a
b
V0
0
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Current Flow and Conductivity
Grimnes and Martinsen, 2008
E and J are parallel
E and J are not parallel
Isotropic Conductivity Anomaly
Anisotropic Conductivity Anomaly
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Current in Body
Grimnes and Martinsen, 2008
• Voltage, current density and magnetic flux density distributions are generated.
• Electrode position, body shape, body size and conductivity determine them.
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Current in Body
Skin
Bone
Skin
CSF
GM
WM
0.25[A/m2]
0
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Electrode and Contact Impedance
Skin
Electrode-Electrolyte-Skin Interface
Amplifier
John G. Webster, Medical Instrumentation: Application and Design, 3rd. ed.
Underneath the Skin
Electrode Surface
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Two and Four-Electrodes (Simplified View)
ZB
ZC1 ZC2
i
v
ZB
ZC1 ZC2
i
v
ZC3 ZC4
1 2C B CV Z Z Z I BV Z I
V3
V3
V4
V4
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Impedance Measurement
( ) sin( )i t I t
cos , sin
R jX Z
R Z X Z
Z
( ) sin( ) cos sin( ) sin cos( )v t ZI t ZI t ZI t
Real Part (In-phase Component)
Imaginary Part(Quadrature Component)
Phase
Amplitude
Z 0I ZI V
+
_
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Phase-sensitive Demodulation
( ) sin( )i t I t
cos , sin
R jX Z
R Z X Z
Z
( ) sin( ) cos sin( ) sin cos( )v t ZI t ZI t ZI t
Real Part (In-phase Component)
Imaginary Part(Quadrature Component)
( )v t
sin( )t
cos( )t
0
1 T
dtT
0
1 T
dtT
1cos
2ZI
1sin
2ZI
Z 0I ZI V
+
_
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IMM (Impedance Measurement Module)
Digital waveform generator
Phase-sensitive demodulator
DAC
ADC
BPF & Amp
BPF & Amp
DC offset
HCP+
BPF & Amp
IA
I / V12 or 16 bit
16 bit Currentoutput
Voltageoutput
Differentialvoltage input
Currentinput
GIC x 4
FPGA
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BCA (Body Composition Analysis)
1 H HR
S S
2HV SH
R
2
1 2 3
HTBW W
R Total Body Water (TBW):
H
S
Fat Free Mass (FFM): 0.73
TBWFFM
2
1 2
HTBW
R
Body Fat (BF): 2( ) 1
(%) 100 (1 ) 100W FFM H
BFW W R
-
-
2
1 2 3 4
1(%)
HBF A S
W R
H: heightW: weightR: resistanceA: ageS: sex
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BCA (Body Composition Analysis)
x1 + x2 = r1x1 + x3 + x4 = r2
x2 + x3 + x5 = r3x4 + x5 = r4
x1 + x3 + x5 = r5x2 + x3 + x4 = r6
01 1 0 0 11
01 0 1 1 22
10 1 1 0 33
1 40 0 0 14
1 51 0 1 05
0 60 1 1 1
rx
rx
rx
rx
rx
r
Ax r
1( )T T-x A A A r
11 0.5 0.25 0.25 0 0.25 0.25
22 0.5 0.25 0.25 0 0.25 0.25
33 0.5 0.25 0.25 0.5 0.25 0.25
44 0 0.25 0.25 0.5 0.25 0.25
55 0 0.25 0.25 0.5 0.25 0.25
6
rx
rx
rx
rx
rx
r
- -
- - - - - - - -
x1 x2
x3
x4 x5
2
1 2 3 4 5 6
1 1 1(%) ( )
arm trunk leg
HBF A S
W R R R
1 2
1 2
arm
x xR
x x
4 5
4 5
leg
x xR
x x
3trunkR x
Grimnes and Martinsen, 2008
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• ECIS- Real-time, label-free, non-invasive monitoring for live-cell- Functional and morphological change detection using impedance
for the activities of cells
• Culture ware
- Gold film electrodes with an insulating film
- Several electrodes at the base in the well
• Oxygen plasma process
- Clean the electrode and sterilize the chamber
- Improve the adhesion of cells due to hydrophilic
• Diameter of electrode(s): 15 – 500 μm
• Electrodes per well: 1 – 40
• Well volume : 100 – 600 μL
Wegener J, Keese C R and Giaever I, 2000, Electric cell-substrate impedance sensing(ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces, Cell Research, 259, 158-166, www.biophysics.com
ECIS (Electric Cell-substrate Impedance Sensing)
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S. Reitinger et al, 2012 Biosens Bioelectron. Vol. 34 Issue 1 pages 63-69
Inter-digitatedelectrodes
Inter-digitatedmicrosensor electrodes
Inter-digitatedelectrodes
Microelectrode array
E. Sarro et al, 2011 Biosens Bioelectron. Vol. 31 Issue 1 pages 257-263
K. Heileman et al, 2011 Biosens Bioelectron. Vol. 49 pages 348-359
• Impedance spectroscopy for cellular bio-sensing
• Observation of cells
• Measurement of physiological properties of cells
• Non-invasive and real time
Bioimpedance Sensors for Cells
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E. Sarro et al, 2011, Biosens Bioelectron,vol. 31, Issue 1, pp. 257-263.
Monitoring of Cellular ConcentrationP.O. Bagnaninchi et al, 2011, PNAS 108, pp. 6462–6467.
Monitoring of Cell Differentiation
D. Opp et al, 2009 Biosens Bioelectron, vol. 24, Issue 8, pp. 2625-2629.
Cytotoxicity and Cell Death
Bioimpedance Signals from Cells
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Lead (one or two pairs of electrodes) Design
• How to determine electrode positions for BCA?
• What is a best electrode configuration for bioimpedance
measurement using a wrist band?
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Lead Field, Sensitivity and Transimpedance
Grimnes and Martinsen, 2008
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EOD