Low Cost Dual Frequency Impedance Analysis for Measuring

Internal and External Celluler Fluid

Khusnul Ain

, R. Arif Wibowo

, Soegianto Soelistiono

, Lailatul Muniroh

, Tri Agggono

, and

M.Rizky Yusdy

Biomedical Engineering, Universitas Airlangga, Surabaya, Indonesia

Physics, Universitas Airlangga, Surabaya, Indonesia

Public Health, Airlangga University, Surabaya, Indonesia

Keywords: Bioimpedance, dual frequency, extracellular, intracellular, low cost

Abstract:

The regulation of body fluid balance is a major concern in body health. Disruption of body fluid balance is a

major factor responsible for changes in cell volume. It can affect cell function and survival. Intracellular

fluid (ICF), extracellular fluid (ECF) and total body fluid (TBW) have been used as information on body fat

levels, dengue indications and some chronic diseases. The design and development of dual frequency

bioelectrical impedance analysis prototype are used as a candidate for intracellular and extracellular fluid

measuring instrument. The device was built using sine wave generator from ICL8038 which can produce 20

kHz and 75 kHz voltage controlled current source (VCCS) and from LF412 which can generate 0.5 mA

from Howland dual op-amp method, potential was measured by instrument amplifier from AD620 and

AD536 was used as AC to DC converter. The device performance was tested on 10 volunteers. The

performance indicator is the relationship of ICF and ECF calculations to H

/Z. The analysis of intracellular

fluid (ICF) was obtained from used the measurement of total body impedance at high frequency of 75 kHz.

It has excellent linearity with R² = 0,9636. Meanwhile, analysis of extracellular fluid (ECF) was obtained

from the measurement of total body impedance at low frequency of 20 kHz. It has a very good linearity with

R² = 0.9579..

1 INTRODUCTION

Dengue fever is an acute disease caused by dengue

virus infection carried by mosquitoes Aedes aegypti

and Aedes albopictus. The virus causes disruption of

the capillary blood vessels in the blood clotting

system resulting in bleeding. The dengue virus

transmitted through the bite of Aedes aegypti and

Aedes albopictus was previously infected by dengue

virus from other dengue fever patients with 4 related

antigens, but different serotypes (DENV-1, DENV-

2, DENV-3, and DENV-4) including the genus

Flavivirus, family Flaviviridae (WHO, 2009).

The classification and definition of dengue fever

is divided into dengue fever and dengue

hemorrhagic fever. Dengue fever begins with a

sudden increase in temperature with headache,

myalgia, macular rash, loss of appetite, nausea,

vomiting, abdominal pain, changes in psychological

state, and thrombocytopenia, then if initial clinical

management or appropriate fluid therapy is not

provided, dengue fever will become a dengue

hemorrhagic fever that begins with a fever that

subsides but increases micro vascular permeability,

decreases plasma volume, and is aggravated by

hypotension and shock, lastly if appropriate therapy

is not available, circulatory failure will occur, then

dengue hemorrhagic fever will become dengue

shock syndrome which is a fatal classification and

definition of dengue that begins with a rapid and

weak pulse.

Therefore, delays in the management of fluid

therapy may lead to death (Deen et al., 2006). The

number of cases of dengue fever every year and the

absence of vaccines and antiviral drugs that can stop

dengue virus infection, result in broad loss impact,

especially on economic and health aspects (WHO,

2009). Dengue virus that enters the body will infect

immune cells in the skin tissue then enter the

lymphatic system, thus, triggering a strong

inflammatory reaction. During the incubation period,

the virus replicates locally then spreads into the

504

Ain, K., Wibowo, R., Soelistiono, S., Muniroh, L., Anggono, T. and Yusdy, M.

Low Cost Dual Frequency Impedance Analysis for Measuring Internal and External Celluler Fluid.

DOI: 10.5220/0007545905040510

In Proceedings of the 2nd International Conference Postgraduate School (ICPS 2018), pages 504-510

ISBN: 978-989-758-348-3

bloodstream which is commonly referred to as

viremia. In some patients, especially children,

dengue virus infection can lead to severe clinical

manifestations. The most severe clinical

manifestations can cause blood vessels to become

permeable resulting in leakage of plasma which

ultimately requires intensive hospital care. The

phase and clinical symptoms when experiencing

dengue fever is the first phase of high fever which is

characterized by high fever reaches 40

C with

symptoms caused by severe headache, back pain in

the eyes, nausea, vomiting, swollen glands, rash,

pain muscles and joints. This is a sign that a person

is infected with dengue virus after being bitten by an

infected mosquito and an incubation period of

dengue virus for 4 - 10 days, in this phase usually

occurs for 2 - 7 days.

Accurate diagnosis and monitoring of dengue

fever condition is needed to identify the severity

level in providing appropriate treatment. In order to

handle and control cases of dengue, there are many

methods that have been developed and used to

diagnose and monitor the risk of dengue fever. One

of them is to observe the onset and progression of

plasma leakage of dengue fever patients by

measuring the increase in total hematocit or

hemoglobin (WHO, 2009). The advantage of this

method is not only to diagnose dengue fever but also

to distinguish dengue fever as well, then by

monitoring the number of thrombocyte of dengue

fever patients and liver function. Although this

conventional method has been able to provide an

accurate diagnosis, it takes a long time, is invasive,

and can harm patients, since this conventional

method requires frequent invasive blood sampling,

which can lead to further injury to the subcutaneous

tissues and potentially harmful to people with

dengue fever (Ibrahim et al., 2005 and Ibrahim et

al., 2007). In addition, this conventional method can

only be done in inpatients at the hospital only, but

not all patients with dengue fever can undergo

hospitalization because the facility in the hospital

itself is not able to handle all patients with dengue

fever in a very large number (Ibrahim et al., 2005).

The facts show that cases of dengue fever are

often misdiagnosed with other diseases, such as flu

or typhoid. This is because the symptoms of dengue

virus infection in the early stages may not have a

distinctive feature (Ginanjar, 2008). So far, the

majority of society and health practitioners in

Indonesia still do not understand the difference

between fever caused by dengue virus infection and

common fever caused by other infections. This is

what causes the number of morbidity (mortality rate)

and mortality (Mortality Rate), because the success

of the handling of dengue fever case is largely

determined by early detection of dengue virus

manifestations in patients so that it can be done case

management in the form of management therapy

effective fluids. Early detection of dengue fever

patients with non-invasive method, one of them can

be done through body temperature analysis because

at the time of dengue fever patient experiencing high

fever phase until critical phase, they will have fever

which has characteristic marked with horse saddle

graph produced by body temperature.

Multi-frequency bioelectrical impedance analysis

(MF - BIA) method can diagnose the manifestation

of dengue virus in dengue fever patient. This method

uses a constant electric current at low frequencies of

5 kHz to 1000 kHz through the body, and produces a

potential difference value (V) to obtain an

impedance value (Z), using four electrodes (Jaffrin

et. al., 2008). The results showed that there was a

correlation between the frequency value of body

fluid measurements, where the low frequency values

represent extracellular fluid values (ECF) and high

frequency values represent intracellular fluid values

(ICF), so the total body water (TBW) was obtained

based on the sum of the fluid value extracellular

(ECF) and intracellular fluid value (ICF). Several

studies have been conducted to determine the

intracellular and extracellular fluids (Moissl et al.

2006).

2 METHODS

In this research, the design and development of

intracellular cell and extracellular cell impedance

measuring device. The design of the device is shown

in Figure 1.

Figure 1 : Block diagram of Bioelectrical Impedance

Analysis

Low Cost Dual Frequency Impedance Analysis for Measuring Internal and External Celluler Fluid

505

The device consists of a sine wave generator,

VCCS, voltage meter and microcontroller. Sine

wave generator circuit was used as a generator of

sinus voltage signal using IC IC8080 which was

then connected with resistor and capacitor to

produce sine voltage of 20 kHz and 75 kHz which

can be seen in Figure 2.

Figure 2 : Design of sine wave generator

Voltage Controlled Current Source (VCCS)

circuit functions as electric current source based on

input voltage signal. The VCCS circuit uses a dual

opamp built from IC LF412 coupled with a resistor

that can serve as a current source of 0.5 mA, as

shown in Figure 3.

Figure 3 : Design of Voltage Control Current Source

(VCCS).

The Instrument Amplifier circuit was used as a

comparison of two input voltages into one output

using IC AD620 which is then connected to the

resistor as a reinforcement source, as in Figure 4.

Figure 4 : Design of Instrument Amplifier

3 RESULT

Sinus generator built from IC IC8080 was coupled

with capacitor 10 nF, resistor of 1650 Ω and 440 Ω

respectively to produce sine voltage of 20 kHz and

75 kHz. The output signal generated by the circuit

can be observed through the oscilloscope, as shown

in Fig. 5 and Fig. 6.

Figure 5 : Signal 20 kHz from sine wave generator

Figure 6 : Signal 75 kHz from sine wave generator

The output signal of the sine wave generator

circuit produced a direct voltage (DC) that fluctuated

from 4.80 V until 7.84 V. The VCCS circuit was

used as an electric current generator based on input

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voltage using LF412 IC. The circuit requires a

supply voltage of ± 15V and a resistor to produce an

electric current with a frequency of 20 kHz and 75

kHz with an electrical current ≤ 0.5 mA that is safe

for the body. The output signal generated by the

VCCS circuit can be observed through the

oscilloscope shown in Figure 7.

Figure 7 : The signal output from VCCS circuit

Based on the signal in the oscilloscope, it can be

seen that the output signal from the VCCS circuit

was a DC electric current that fluctuated from 3.52

V to 6.56 V. Furthermore, the VCCS circuit test

showed the electric current generated against the

load changes given in Figure 8.

Figure 8. Graph between current and load at 50 kHz

The instrument amplifier circuit serves as a

comparator of two inputs voltage into one output

voltage. The circuit used an IC AD620 and ± 15V

supply voltage connected to the resistor as the

amplifier. The circuits used to tap the potential

difference of the body from the electric current 20

kHz and 75 kHz. The circuits were channeled into

the body using disposable electrodes that were

bonded on the body surface. Based on the results

shown in the oscilloscope, it appears that the output

signal of the instrument amplifier circuit produced a

DC voltage that fluctuated from 3.84 V to 7.36 V.

The amplification of the instrument amplifier circuit

is 1.5 as shown in Table 1.

Table 1 : Test of instrument amplifier

The signal generated by the instrument amplifier

circuit can be observed through the oscilloscope, as

displayed in Figure 9.

Figure 9 : Output signal from Instrument Amplifier

Dual frequency of bioelectrical impedance

analysis tool as diagnostic candidate of dengue fever

consists of hardware and software. The hardware

was used as a generator of 20 kHz and 75 kHz sine

wave signals with an electric current of ≤ 0.5 mA.

Furthermore, the electric current was used to

determine the impedance (Z) of the body.

The measurement of the potential difference (V)

generated from the 20 kHz and 75 kHz sine wave

signals was received by the instrument amplifier and

processed by arduino uno microcontroller with the

software. The software functions as a viewer and

Low Cost Dual Frequency Impedance Analysis for Measuring Internal and External Celluler Fluid

507

data processor obtained from hardware. The

software will read the potential of the body. The

analog data were converted into bits. The bit was

converted by arduino software IDE 1.6.9 into a volt /

potential (V), the last result of the measurement of

the potential (V) was processed by the software into

an impedance using Equation (1).

Equation 1 was obtained based on Figure 10.

Figure 10 : Analogies of conventional calculations

The measurement of body impedance (Z) using

Equation (1) was conducted by dividing the injected

electric current (I) and the potential body (V)

obtained from the instrument amplifier circuit. The

problem that occurred when measuring the body

impedance (Z) using equation (1) was when the

electric current (I) was considered constant, because

in fact in testing the voltage controlled current

source (VCCS) circuit in which the electric current

(I) is smaller when the load gets bigger. So when

measuring the body impedance (Z) using equation

(1) and assuming the value of electric current (I)

constant at ≤ 0.5 mA, the resulting body impedance

(Z) is not valid. Voltage divider approach is a valid

method that can be used in measuring body

impedance (Z), that is by using equation (2).

Equation (2) was obtained from Figure 11.

Figure 11 : Analogies of modification calculations

The measurement of body impedance (Z) using

equation 2 was done by dividing the voltage (Vo)

obtained from the reading of the potential at meeting

point (R) and (Z) and the voltage of the current

source Vs obtained from the reading the potential at

point (R) then multiplied by the resistance (R) used.

The results of device testing with variations of

measurable barriers can be seen in Table 2 and 3.

Tabel 2 : Device testing with various loads at 20 kHz

Tabel 3 : Device testing with various load at 75 kHz

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After the device was well-tested, it was used to

measure impedances of 10 volunteers at frequencies

of 20 kHz and 75 kHz. The data test were taken by

measuring weight, height, and total body impedance.

The data were then used to determine the

intracellular fluid (ICF), extracellular fluid (ECF),

and total body water (TBW), while the results of

data retrieval device that has been done can be seen

in Table 4.

The measuring body fluids is based on the

equation obtained by Hoffer et al., in his journal

entitled Correlation of Whole - Body Impedance

with Total Body Water Volume (1969). The

equation relates between total body impedance and

total body fluids calibrated by dissolution techniques

tritium in-vivo. Furthermore, the equation was used

on 10 Volunteers. This is the example of the x

volunteer:

• Height (H) = 168 cm

• Weight (W) = 70 kg

• It is obtained impedance (Z) = 937 Ω when

Frequency was 20 kHz and impedance (Z)

= 682 Ω was obtained when Frequency was

75 kHz

The calculation of intracellular fluid (ICF),

extracellular fluid (ECF), and total body water

(TBW), along with percentage of intracellular fluid

value (ICF) and extracellular fluid (ECF) to total

body fluids (TBW) is,

• Intracelular Cell Fluid (ICF)

Y = 0.5855(X) + 1.9878

ICF = 0.5855 x (168

/682) + 1.9878

ICF = 26.22

• Extracelular Cell Fluid (ECF)

Y = 0.5855(X) + 1.9878

ECF = (0.5855 x (168

/937) + 1.9878)

ECF = 19.62

• Total Body Water (TBW)

TBW = ICF + ECF

TBW = 26.22 + 19.62

TBW = 45.84

• Percentage of ICF and ECF

¾ Percentage of ICF

%ICF = (ICF/TBW) x 100%

%ICF = (26.22/45.84) x 100%

%ICF = 57%

¾ Percentage of ECF

%ECF = (ECF/ TBW) x 100%

%ECF = (19.62/45.84) x 100%

%ECF = 43%

The results of data collection analysis from 10

volunteers to be shown on the graph and linearity

graph between H

/Z and intracellular fluid (ICF) and

extracellular fluid (ECF) which can be seen in Table

4 and Figure 12 and 13.

Tabel 4 : Data device and analysis

Figure 12 : Graph of linearity between H

/Z and ICF

Figure 13 : Graph of linearity between H

/Z and ECF

4 CONCLUSIONS

The dual frequency bioelectrical impedance as

diagnostic candidate for dengue fever patient can be

used to monitor the percentage of intracellular fluid

(ICF) and extracellular liquid (ECF). The

intracellular fluid (ICF) was obtained from the

measurement of total body impedance value at high

frequency (75 kHz) with linearity of R² = 0.9636

and extracellular liquid (ECF ) was obtained from

the result of measuring total body impedance value

Low Cost Dual Frequency Impedance Analysis for Measuring Internal and External Celluler Fluid

509

at low frequency (20 kHz) with linearity of R² =

0.9579.

REFERENCES

Deen J et al. 2006. The WHO Dengue Classification

and Case Definitions : Time for a

Reassessment. Lancet., 368 : 170 – 173.

Ginanjar, Genis. 2008. Demam Berdarah, a Survival

Guide. Yogyakarta : B – First.

Hoffer et al. 1969. Correlation of Whole – Body

Impedance with Total Body Water Volume. J.

Appl. Physiol, 27, 531 – 534.

Ibrahim et al. 2005. A Novel Approach to Classify

Risk in Dengue Hemorrhagic Fever (DHF)

Using Bioelectrical Impedance Analysis (BIA).

IEEE Transactions On Instrumentation And

Measurement, Vol. 54, No. 1.

Ibrahim et al. 2007. A New Approach to Classify

Risk in Dengue Infection Using Bioelectrical

Impedance Analysis. Dengue Bulletin – Volume

31.

Jaffrin et al. 2008. Body Fluid Volumes

Measurements by Impedance : A Review of

Bioimpedance Spectroscopy (BIS) and

Bioimpedance Analysis (BIA) Methods. Med.

Eng. Phys., 30, 1257 – 1269.

Moissl et al. 2006. Body Fluid Volume

Determination via Body Composition

Spectroscopy in Health and Disease. Physiol.

Meas., 27, 921 – 933.

World Health Organization. 2009. Dengue :

Guidelines for Diagnosis, Treatment, Prevention

and Control. Switzerland : WHO Press.

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