Design a Portable Bio-Sensing System for Glucose ... - IEEE Xplore

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Jui-Lin Lai, Han-ning Wu, Hung-Hsi Chang, and Rong-Jian Chen. Mixed-Signal Integration Circuit Design Laboratory. Department of Electronic Engineering,.
2011 International Conference on Complex, Intelligent, and Software Intensive Systems

Design a Portable Bio-Sensing System for Glucose Measurement Jui-Lin Lai, Han-ning Wu, Hung-Hsi Chang, and Rong-Jian Chen Mixed-Signal Integration Circuit Design Laboratory Department of Electronic Engineering, National United University Miao-Li 36003, Taiwan [email protected], [email protected], [email protected] Abstract—In the paper, the electrochemical sensor consists of the potantiostat with glucose test strip electrode and the automatic test system to readout the electronic signal related to the concentration of Glucose is proposed. The structure of an Opbased potentiostat is improved, analyzed, and implemented. The working operations are very complicated, and having some processing property. These performances will directly influence to oxidation-reduction reaction through the cyclic voltammetry bounded from 0.4V to -1.4V is applied on the three-electrode. The readout circuit of potentiostat is successfully designed and simulated by HSPICE. The readout data is automatically accessed by the NI DAQ card and the coordinated Labview programming the test schedule to control the related instrumentation with GPIP to obtain the experiment result for various glucose concentrations. The glucose detection system associated with the improved Op-based potentiostat and an automatic test system is realized. The objective of this paper was to investigate the improved OP-based three-electrode potentiostat used in electrochemical glucose biosensor system to obtain more accuracy the measurement results. The experiment result show that the potentiostat is produced more linearity output range of voltage from 4.4V to 0.6V corresponding to the measured concentration of glucose due to 50-600mg/dl range, respectively. The architecture of the potentiostat can be intergraded for VLSI design. There have a great potential in the portable bio-detection system for the health-care and bio-medicine applications.

reference electrode, which is related to the concentration of the electro-active analytic in the solution. Two-electrode (RE and WE) Potentiostat is used to detect the glucose may be produced the phenomenon of concentration polarization and the larger level of voltage at RE terminal. The induced current flow through RE electrode produced the offset voltage that the measurement error is increased [8]-[11]. The CE electrode is used in Potentiostat which is a three-electrode bio-sensor have properties with fast sense, more efficiency and reliable. The CE electrode provides a current loop and RE electrode form a voltage path to make the over-voltage affect in RE that the measurement error is improved [12]-[15]. The electrochemical reaction on the electrode is detected as a current proportional to the concentration of substrate. The Potentiostat are the electronic interface to a large category of Amperometric sensors which are capable of detecting many biologically and environmentally important analytics. Those Potentiostat and interface circuits are integrated in CMOS chip to increase the functionality and reduce the system size to be implemented in the system-on-chip (SoC) designs for CMOS technology [10]-[11]. The widely used electrochemical glucose bio-sensor with electron propagation mediator are the oxygen electrode-based (O2-based) sensor to product the oxidation current and the hydrogen peroxide electrode-based (H2O2-based) sensor to induce the reduction current. The Potentiostat is designed to amplify and readout those current in the bio-signal detection system. The basic configuration is included a three-electrode Amperometric electrochemical sensor, the current meter, and a control amplifier, is shown in Fig. 1 [8]. The electrochemical sensor relative reaction is based on the potential between the counter electrode (CE) and reference electrode (RE) by the control amplifier at a desired cell potential, Vcell that the working electrode (WE) is response a current dependent on the concentration of under test. Assume the potential at WE is high than RE, then the oxidation current from WE flow into RE. Inversely, the potential at RE is high than WE is called the reduction current. The number of ionic within the surface of work is sensed by electrode glucose sensor corresponding to the concentration of glucose. Many companies and research laboratories are involved in manufacturing, testing, and researching biochips.

Keywords- potentiostat, Glucose electrochemical, bio-sensors, carbon-electrode, enzyme

I.

INTRODUCTION

The enzymatic electrode of glucose oxidase is proposed by Clark and Lyons at Cincinnati, Ohio, 1962. In 1973, Guilbault and Lubrano used the Amperometric in the electrochemical to sense the volume of hydrogen peroxide (H2O2) to know the concentration of glucose [1]-[5]. The electrode without enzyme membrane to determine the glucose concentration base on the surface reaction of the metal is reported. Need a new material is used in the metal [6]. The various glucose monitor is reviewed [7]. The Amperometric is the more used technology but it is more difficult for circuit deign and unsuitable for long term measurement. How to design an Amperometric with a high impedance amplifier is an impotent issue. The transducer measured flowing current signal between a biochemical sensitive electrode and a 978-0-7695-4373-4/11 $26.00 © 2011 IEEE DOI 10.1109/CISIS.2011.20

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Figure 2. Equivalent circuit of an electrochemical cell

B. Op-based three-electrode Potentiostat The three-electrodes Potentiostat is consisted of the electrode, the trans-impedance amplifier, control amplifier, and buffer as described in Fig. 3. The negative feedback structure is constructed from the control amplifier OP2 and the buffer OP1 that the potential at RE terminal is controlled by Vsrc, that is, VRE = -Vsrc. The property of OP1 with highinput impedance is ensured a few current flows through the RE to hold the constant voltage. The potential at WE terminal is a virtual ground for the trans-impedance amplifier OP3, is equal to zero volt. The potential difference between RE and WE to hold a constant value isn’t affected by the induced current signal. The control amplifier is provided a current path flow-through CE and WE but not current branch into RE. The sensed current directly flow Rf is produced output voltage from the trans-impedance amplifier, is proportional to the concentration of under-test solution. [15]

Figure 1. Basic concept for three-electrode measurement circuit

The objective of this paper was to investigate the improved OP-based three-electrode Potentiostat used in electrochemical glucose biosensor system to obtain the measurement results with the better linearity. In addition, the detection system is associated with Potentiostat, DAQ interface card, and Laboratory Virtual Instrument Engineering Workbench (LabView) graphic control software to integrate the automatic test system. The proposed portable bio-detection system can rapid and easy to complete the glucose measurement. II.

STRUCTURE OF POTENTIOSTAT

The Potentiostat is integrated with the Amperometric electrode and the transducer to sense the response current. The Amperometric glucose biosensor combines two advantages: the high activity, the stereo selectivity of the enzyme catalyst with respect to a given substrate with the versatility of the electrical measurements. The electrochemical electrode of Amperometric sensor is integrated the Potentiostat in biosensor system. The configuration is divided into two types, such as an OP based and current-mirror based three-electrode Potentiostat [5],[8]-[10],[15]. Whenever the current-type Potentiostat must be solved two things: (1) Fix potential between WE and RE, (2) Make a current loop from WE and CE and readout this current value. A. Equivalent Circuit of Electrochemical Cell The Potentiostat is used to translate the reaction of electrochemical into the volume of electronics. In order easy to simulation the function of the bio-detection circuit. The equivalent circuit of Amperometric sensor is adopted by an Electrochemical Impedance Spectroscopy (EIS) experiment that it is more simplified than the really used electrochemical cell, is shown in Fig. 2 [8]-[10]. The capacitors CCE and CWE are expressed the double layer capacitor of CE and WE, respectively. RCE, RRE, and RWE express the charge-transfer resistances of CE, RE, and WE, respectively. RS1 and RS2 express the solution resistance.

Figure 3. The used OP-based potentiostat

The shifter circuit is added in the OP-based Potentiostat to construct the improved Potentiostat structure to satisfy the both measured oxidation current and reduction current can readout. Where OP1 is a trans-impedance amplifier; OP2 is a buffer; OP3 is control amplifier; and OP4 as a sum amplifier that the output voltage level range based on the various concentration was shifted from the lower level mapping to high in order to match the system requirement. The accuracy and the range of measurement are improved. The RC filter is used to reduce the measure noise. The measurement circuit is integrated the charge-transfer resistance of electrode base on Eq.2 in progress the simulation and the practically measurement to verify the function of the Potentiostat test configuration. The induced current is input to the operational amplifier OP1 and the converted voltage is

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output from the operational amplifier OP4 in the Potentiostat of the test system.

sensor is expressed in Fig. 6. After the whole system is steady, the standard solution of certain concentration glucose is added. At the same time, the glucose will diffuse around enzyme electrode to produce H2O2, and the chemical reaction can be induced the oxidize current to measure the various concentration of glucose.

The working operations are very complicated, and having some processing property. These performances will directly influence to oxidation-reduction reaction through the cyclic voltammetry method is supplied the difference voltage level to view the responded current on the three-electrode, the I-V characteristic curve is shown in the Fig. 4 [2]-[3]. The voltage levels are bounded from 0.4V to -1.4V. The adjusted output level is fitted the input data range of micro controller unit.

VRE

Vox u

R2 R2  R3

(1)

The dashes line part expressed the simplified equivalent circuit model of the electrode in the Fig. 3. The solution resistances and the double layer capacitors are very small can be ignored. The charge-transfer resistances is calculated by

Rwr

Vox I sensor

Figure 5. Diagram of chemical reaction in biosensor

(2)

Figure 6. Glucose oxidase measurement reaction [3]

The glucose oxidize (GOD) convert the glucose into the lactones species (glucono--lactones) and the hydrogen peroxide (H2O2). [14]

Figure 4. Oxidize- reduction reaction [9]

III.

MEASUREMENT SYSTEM STRUCTURE

Glucose O2  2 H 2 O GOD  o gluconicacid  2 H 2 O 2

The bio-detection system associated with the improved Op-based Potentiostat and the automatically test system for glucose is realized. The electrochemical reaction operation of bio-electrode is decided the range and type of the acquired response signal by the test system. The automatically test system is programmed by PC with Lab-View software or microcontroller clearly to display the measured result. The proposed system has been implemented the portable biosensing system for glucose detection.

(3)

-D-Glucose+GODox(GOD-FAD)D-glucono--lactones +GODred(GOD-FADH2) (4) where D-glucose, per-oxidize from horseradish and odianisidine dihydrochloride were all purchased in powder form from Sigma-Aldrich, USA. The glucose is oxidized, and the mediator is enervated by Ferro+2 for the electron propagation, then Ferro+2 diffuse to the surface of enzyme electrode, and the oxidized current is reacted, namely: 2Ferri+3 + GODred  2Ferro+2 + GODox + 2H+ (5)

A. Electrochemical Reaction in Bio-sensor The electrochemical reactions in the developed biosensor are shown in Fig. 5. The general structure of glucose sensor was employed the mediator to overcome oxygen limitation. The electron mediators commonly used are ferro/ferricyanide, hydroquinone, ferrocence, and various redox organic dyes [6]. Take the enzyme electrode with GOD (Glucose Oxidase) to the mixed phosphate buffer (Ph=7.0), and supplied certain voltage to the dedicate bio-sensor. The electrode with GOD is accepted or provided electron depends on the oxidation or reduction response. The reaction of GOD enzyme membrane in the bio-

Ferro+2  Ferri+3 + e¯ (6) After Ferro+2 are oxidized, the number of electrons is given off in the solution. The produced electrons were formed the certain magnitude of currents. The values of the currents are proportional to the oxidation of Ferri+3 on the surface of electrode. And the generated Ferri+3 are elated with the concentration of the added glucose. As the result, we can measure the glucose content in the solution was sensed the values of currents by the enzyme bio-electrode.

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the commercial strip, is stored in EEPROM and displayed in LCD module. The overall system is integrated by the individual IC chip on the PCB, is shown in Fig. 10. The portable glucose bio-sensor system is realized.

B. PC-based Measurement System The test configuration is consisted of the OP-based Potentiostat with the regulated power supply circuit, the glucose electrode, data acquisition device and personal computer with GPIB interface, and Lab-View Software, is shown in Fig. 7. The improved OP-based Potentiostat is adopted the commercially OPA devices to implement on the PCB. The readout data is automatically accessed by the NI DAQ card (USB-6009 with 8 channels, 12bit ADC, 48 KHz sample rate) through GPIB input to PC. The coordinated LabView programming the test schedule to control the related instrumentation with GPIP to obtain the experiment result for various glucose concentrations is provided. Using graphiclanguage to realize the data flow express the execution sequencing of program. The application software is consisting of four flows for the measured signal access, result display, file open, and store to process the measurement operation in the bio-sensing system, is shown in Fig. 8.

Figure9. System block diagram

Power Module Sensor

Our Readout Circuit

Labview /PC

Data

Figure7. Measurement system structure

Figure 10. Practically measurement system

IV.

SIMULATION AND EXPRIMENT RESULTS

The proposed Potentiostat test configuration is used the macro model of commerce device and the equivalent model of electrode to simulate the function. The readout circuit with the linearity of oxidation/reduction current and the rail to rail amplification are verified by HSPICE for TSMC CMOS technology. As the simulation results show that the output voltage of the circuit is produced for the oxidation current range from 80pA to 50uA, is shown in Fig. 11. The variation range of output voltage is very linearity during the responded current range. The circuit has a rail to rail output. Figure8. Programming the test schedule

Only DC analysis simulation doesn’t enough response the really state. Since the solution resistance is changed follow the difference time for a specific concentration of glucose, that is, the current is a time variant function. When the measurement operation progress with glucose concentration is start up, the output voltage Vout is going to +Vmax/-Vmax for each times the oxidase/reduction reaction. The response curve is gradually falling or rising to reach the steady-state value corresponding to measure concentration of glucose. Therefore the transient response of the output current for oxidation and reduction are simulated in the time domain during response

C. Microcontroller-based Measurement System System hardware consists of the Potentiostat circuit, the digital control circuit, and the data display and store circuits, is shown in Fig. 9. The Potentiostat circuit senses the responded current from bio-sensor by the readout circuit to output a voltage signal into microcontroller. The digital control circuit is designed based on ATMEGA 16L for ATMEL product. The measured analog signal is converted by A/D conversion in the microprocessor. The calculated glucose level is measured from

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time, are shown in Fig. 12 and Fig. 13, respectively. The readout data is latched until the data reach steady-state.

Figure 15. Block-diagram for test schedule and front panel Figure 11. Oxidation current Vs. output voltage

Figure 12. Transient response for oxidase current Figure 16. Output voltage Measured during response time

Figure 13. Transient response for reduction current

Figure 17. Output voltage measurements for various glucose concentrations

A completely Amperometric sensor used in the practically test measurement system for the glucose detection. The used screen-printed carbon paste electrode strip is assembled with immobilized glucose oxidase containing a nitrocellulose strip from the commercially product by the Bioptik Technology Inc. The standard test solution is disposed by the PBS 7.2 and D-(+)-Glucose. The glucose sensor senses the ionic within the surface of work electrode corresponding to the concentration of glucose, then the responded current flow in the Potentiostat and output the voltage signal from the detection system. The automatic test configuration is consisting of the software program (Lab-View) and data acquisition (NI DAQ card). The system is automatically catching the outputted data from the Potentiostat for the under-test concentration of the glucose. The measured result is stored in the test data-base. The human interface is used the Lab-View program to programming the front-panel for the control panel and the display panel, is shown in Fig. 14. The test environment is

Figure 14. Human-interface for Automatic measurement system

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REFERENCES

directly set-up from the front panel. The acquired data is expressed in the window of the desired front-panel that the test function is verified by any input data. The test schedule is included the clock generator, counter, signal catch, time detect, save file, and open file modules, is shown in Fig. 15. The measured voltage is latched by signal catch module to store into the save file module due to counter module is matched the desired time.

[1] [2]

[3]

The measurement result shows that the steady-state voltage is produced after 15 second as the dash-line express in Fig. 16. That is, after 15 second, the measured data is catch for each test operation. The effectively experiment data is measured by the glucose measurement system for the various glucose concentration. Those measured data corresponding to the various concentration of glucose are collected to mark the X-Y figure, is shown in Fig. 17. As the experiment results to know that the measurement data is very close to linear during the glucose concentration from 50mg/dl to 600mg/dl. The electrochemical sensor is adequately used in the proposed glucose detection system.

[4] [5] [6]

[7]

[8]

CONCLUSIONS

[9]

The electrochemical enzyme-immobilized test strip is used to sense the glucose concentration by the improved OP-based Potentiost in the bio-detect system. The electrode is responded the current to proportional the concentration of glucose activity. The function of oxidation and reduction is controlled by the polarity of VOX. The range of measurement is changed by the difference value of Rf. Using commercial Op-amp to realize the improved OP-based Potentiostat can product the voltage of response range from 4.4V to 0.6V corresponding to the measured the concentration of glucose for 50-600mg/dl range, respectively. The measurement result shows that the steadystate voltage is produced after 15 seconds. The improved OPbased three-electrode Potentiostat is used in electrochemical glucose biosensor system to obtain the performance with more high-linearity for measurement results. The front-panel of the glucose detection system with DAQ interface and Labview programming to provide the automatic test system is implemented. The proposed detection system can rapid and easy to use for the completely glucose measurement. The portable system should have some properties for low cost, fast response, more accuracy, and simple calibration procedures in the real operation closer to practical application.

[10]

[11]

[12]

[13]

[14]

[15]

ACKNOWLEDGMENT This work was supported by the National Science Council of the Republic of China under the contract NSC-992221-E-239-032.

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