International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 INTERNATIONAL JOURNAL OF ADVANCED RESEARCH IN 6480(Print),

, ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

ENGINEERING AND TECHNOLOGY (IJARET)

ISSN 0976 - 6480 (Print) ISSN 0976 - 6499 (Online) Volume 3, Issue 2, July-December (2012), pp. 145-152 IAEME: www.iaeme.com/ijaret.html Journal Impact Factor (2012): 2.7078 (Calculated by GISI) www.jifactor.com

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INTEGRATION OF BIOSENSORS IN THE BIOMEDICAL SYSTEMSCHOICES AND OUTLOOK

M.Rezki1, 3, A.Belaidi2, T.Benabdallah 1, M.Ayad3 med_rezki@yahoo.fr 1 Industrial Product and Systems Innovation Laboratory, E.N.S.E.T, University of Oran, 31000, Algeria. 2 Department of ele ctroni c, E.N .S.E.T, University of Oran, 31000, Algeria. 3 Department of technicals sciences, University of Bouira, 10000, Algeria.

ABSTRACT The purpose of this paper is to present the recent technological and methodological evolution of biosensors especially their integrability. Although there are several technologies for biosensors, miniaturization and automation seem to be the most advantageous. This is one of the issues addressed in this work. Indeed, the condition for the integration of biosensors - in general with matrix form-, is among the most critical criteria to choose from. To do this, our study will present the criterias for integration of biosensors and the use of "Lab. On. Chip "as an example of an integrated cell biosensors almost perfect and seems to be promising future technology. In addition, we briefly review the thermal properties that may affect the integration of biosensors. Keywords: Biosensors, integration, Lab.On.Chip, electrochemical cells, selection 1. INTRODUCTION The importance of biosensors is clearly demonstrated. It affects a number of areas: biomedicine (diagnostic, medical monitoring, pharmacy), chemical engineering and biochemistry (nutrition, environment, etc.). The need to develop fast and the robust standards required in the areas mentioned necessitate the use of microelectronics because it offers possibilities of micro manufacturing and automation that reduce the production costs. The biosensor is an analytical component made to convert biologic signal to an electrical signal that can be digitized easily in order to be integrated in an acquisition line of data. The latter being the key element of the whole system allows us to choose small sensors that can be transported and integrated with the electronic of command and processing [1] (figure 2).

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International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 6480(Print), ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

Fig. 1 Components of a biosensor [2]

Fig.2 Schematic of a biosensor with a minimal environment. This technological trend of components miniaturization is established and also goes beyond the anticipations of the Moores law (figure 3).

Fig.3 Moores law (originally the law has stipulated that we can double every two years the density of electronic components in the same surface) [3].

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The acquisition line of data is a shown in the figure 04:

Fig. 4 Generalized chain acquisition of a biosensor [4] 2. CLASSIFICATION OF BIOSENSORS a. According to the technology of the transduction The type of biological recognition determines the used type of transduction. Among several modes of transduction, we mention: - Calorimetric: the temperature change caused by biological reactions of bioreceptors is translated into an electrical signal. - Electrochemical cells: It uses the process of recognition ionic liquid environment, there are many techniques in this detection such as: conductometry (either by the detection of conductivity change or by measure of PH), potentiometric measure (it is the detection of potential change of constant currant), ammeter (detection of current change to potential constant), metallic electrodes (transmitting the effect of attachment of an electro active substance such as gold and platinum), electronic techniques (structures EIS, ENFET, CHEMFET, ISFET, TFT and others). - Optics: The optical spectrum of light is detected using optical fibers. - Mass variations: we use the piezoelectric effect; generally, quartz translates a biological change of surface into frequencies change. There are other piezoelectric operations using acoustic waves such as the SAW (Surface Acoustic Waves). b. According to function We have: 1. Enzymatic sensor: these sensors employ receptors that immobilize the enzymes. 2. Immunosensors: it is the result of antigen-antibody reaction since we know that the immune system produces specific antigens against strange bodies (bacteria, viruses, etc.). 3. Microorganisms (Living sensors): these sensors use living tissues as selection receptors. 4. ADN Sensors and bio chips: these sensors are made to detect and/or identify blocks of ADN sequences. Recall that the electronic sensors start replacing gradually the purely biological sensors that use the detection techniques along with marking. 3. BASIC CHARACTERISTICS OF A BIOSENSOR We mention: - Linearity: the calibration curve of bio-sensor must be the most possible linear in the entire area measure and even for strong concentration of the analyte. - Selectivity: aptitude to give correct result having the least possible interference for different chemical substances.
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International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 6480(Print), ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

- Sensibility: it is a response value of an electrode for a given concentration. - Response time: the required time to reach 95% of the response and it must be minor. - Reproducibility: it consists of obtaining almost the same result with the same biosensor according to various different methods and even with different operators. - Biocompatibility: it is the biosensor ability of being efficient in adequate response to a specific application (example: a special chemical to be detected). 4. THE BIOSENSOR REAL DIFFICULTIES Actually, we face many problems which may affect the development of biosensors. Among them we mention the following [5]: - The choice of adequate receptor as well as good transducer for various analytes. - The insufficient development of immobilization technologies on the sensors areas (biosensors) - Instability during the operation of the use of biosensor because of the span time which can last many hours. - The existence of analytes interference. - Incoherent development of the techniques of fabrication, stock, processing, calibration and with least cost. 5. CRITERIA FOR SELECTION OF AN INTEGRATED BIOSENSOR a. Benefits of integration The integration provides many advantages [6]: - Miniaturisation. - Reduction of energy consumption. - Reduced costs due to the possibility of mass production. - Improved reliability by reducing the number of connections. - Best immunity to noises. b. Applications of the selection criteria of integrated sensor In addition to the basic characteristics of a biosensor which are selection criteria, we have other criteria such as: compatibility with the integrated electronic circuits (ICs), the low cost and the dimensions. But we will focus on drawbacks as criteria summary of choice and the degree of integrability which gave us the following table (Table 01): c. Example of an integrated sensor the Lab.on.Chip First, lets start by defining the bio chip. It is a matrix of individual biosensors that can be controlled individually and often used for the analysis of multiple analytes.

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International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 6480(Print), ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

Table 1 Obstacles that hinder the application of integrated biosensors Biosensor Type Calorimetric Optic Major inconvenienes [7] - Scope to use relatively small for the enzymes. -The ambient light often causes strong interferences. - The cost of optical fiber is expensive. - Phase indicators need to be removed after a while. -Problem of integration (requires several modules instead of one) - Difficulties in using low frequency. - Instability if the temperature varies. -reproducibility: problems for some electronic techniques. - Average sensitivity often Nernstian especially for the PH type. - Instability if the temperature varies. - Low sensitivity in liquid medium due to the problems of low viscosity. Degree of integrability Low - Low for the usual type optical biosensor SPR (Surface Plasmon Resonance). - Good for the Mach Zender interferometer voice but remains in development. Low

Acoustic (type SAW)

Electrochimical

Very good especially for microelectronic techniques (Isfets, TFT, etc.)

Mass (piezo)

Low

This matrix is integrated into a single box. The Laboratory - on-chip (Figure 05) or "Lab .On. Chip" is a mega bio-chip that integrates more than the biosensors the complement modules such as bioamplifiers etc. It is a multidisciplinary approach we select and it allows us to minimize energy consumption and increase the speed of biochemical reactions. In fact it includes all the benefits of integrated circuits such as the possibility of increased automation and robotics.

Fig.4 Circuit board of Lab-on-a-chip [8] [9] The Lab.On.Chip is used for the study of : ADN, proteins and peptides, cells, antibodies and antigens. It exists in two (02) forms: - CMOS Imaging (optoelectronic technique).
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International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 6480(Print), ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

- Charge Based Capacitive Measurement CBCM (capacitive measure). Le CMOS imaging is more accurate than the CBCM but it has more complex design and more uses than the second.

Fig. 5 Example of a Lab-On- Chip constitution - type CBCM [10] The circuit shown in FIG (05) illustrates the operating principle of CBCM, the capacity can be found using the following equation:
= . .

(1)

IS and IR are the quantities to be measured. The Lab. On. Chip is a recently and growing technology which is in full expansion because it has more features in this integrated device and thus is a quite promising technique. 6. Complement study: effect of temperature and its impact on the biosensors As biosensors treat physiological signals and therefore biological one, we must consider the thermal properties of biological substances. This is another condition in addition to the study of integration. The specificity of heat in the biological field manifests itself in these two parameters: - Thermal conductivity: biological substances can have a large temperature change in its two forms: hypothermia and hyperthermia (cases of a disease for example). We will have a transport of heat energy which is called 'thermal conductivity'. It directly affects the thermal resistance of the material (see figure6).

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International Journal of Advanced Research in Engineering and Technology (IJARET), ISSN 0976 6480(Print), ISSN 0976 6499(Online) Volume 3, Number 2, July-December (2012), IAEME

Fig. 6 Simulated diagram between thermal resistance (RTH) and the conductivity (K) The figure n6 represents this model [11]:

1 2 .

+2 . +2 .

(2)
= . >

If a=b, then:

+2 .

(3)

The data 1 explains the first situation (when ba) and the data 2 says the second (b=a). - Thermal expansion: the Thermal warming of a biological substance often causes an increase in the volume called thermal expansion. These two parameters change more rapidly in solid materials, hence the need for additional thermal study - in addition to the classic study of heat transfer: convection, conduction and radiation- in the design of bio chips and their boxes of heat dissipation.

7. CONCLUSION In this study, we wanted to address a general way the problem of true integration. We have several levels of integration, we can add for example a system of temperature compensation to the biosensor and say that we have an integrated biosensor but it is only a slight integration. From the table n1 we can ascertain the benefits of microelectronic techniques and deduct that they are the most integrable, thus explains the importance of the Lab.On.Chip. In effect, the researches continue in the integration of sensors in general, but for the biosensors specially. The essential difficulty still resides on the necessity to have a coherent development in several disciplines (biology, chemical, electronics, software, etc.). So its a continuing multidisciplinary research which is imposed.
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8. REFERENCES Hassibi A, Yang Liu & Robert W, IEEE Xplore. Restrictions apply Progress in biosensor and bioelectronic simulations, new application for TCAD , SISPAD 2008, Lake Hakone, Japan, (2008) 10-14. 2 http://www.dddmag.com/images/0409/hts1_lrg.jpg 3 http://www.astrosurf.com/luxorion/Sciences/loimoore-2010.gif 4 Jacob Fraden, Handbook of modern sensors: physics, designs, and applications, Editor: Springer, third Edition, p.4, 2004 5 Gabor Harsanyi, Sensors in Biomedical Applications- Fundamentals Technology and Applications-, Editor: CRC- Press, p.226, 2000. Norbert Noury, Du signal linformation: le capteur intelligent, Exemples industriels et en mdicine, HDR, Universit Joseph Fourier Grenoble 1-7, 2002. 6 L.M.Lechuga, A.Calle and C.Dominguez, Integration of bio, nano, micro and cogno in biosensor devices for human health applications, Superficies y Vacio 18(4), 1-6, 2005. 7 www.nsbri.org/NewsPublicOut/Photos/lab-on-a-chip.jpg 8 www.chem.agilent.com/cag/feature/8-98/ feature_graphics/chip.jpg 9 Mohamad Sawan et al, Laboratory- on-chip based sensors, capacitive measurements, Ecole Polytechnique MONTREAL, p.2, March 2011. 10 Website (1996): www.systemplus.fr/documents/96analyseperfinterco.pdf.
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