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Integration of biosensors in the biomedical systems choices and outlook
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Integration of biosensors in the biomedical systems choices and outlook
1. INTERNATIONAL JOURNAL OF ADVANCED RESEARCH IN 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 ENGINEERING AND TECHNOLOGY (IJARET)ISSN 0976 - 6480 (Print)ISSN 0976 - 6499 (Online) IJARETVolume 3, Issue 2, July-December (2012), pp. 145-152© IAEME: www.iaeme.com/ijaret.htmlJournal Impact Factor (2012): 2.7078 (Calculated by GISI) ©IAEMEwww.jifactor.com INTEGRATION OF BIOSENSORS IN THE BIOMEDICAL SYSTEMS- CHOICES AND OUTLOOK M.Rezki1, 3, A.Belaidi2, T.Benabdallah 1, M.Ayad3 firstname.lastname@example.org 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 technical’s 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 criteria’s 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  (figure 2). 145
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  Fig.2– Schematic of a biosensor with a minimal environment.This technological trend of components miniaturization is established and also goes beyondthe anticipations of the Moore‘s law (figure 3). Fig.3– Moore’s law (originally the law has stipulated that we can double every two years the density of electronic components in the same surface) . 146
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), © IAEMEThe acquisition line of data is a shown in the figure 04: Fig. 4– Generalized chain acquisition of a biosensor 2. CLASSIFICATION OF BIOSENSORSa. According to the technology of the transduction The type of biological recognition determines the used type of transduction. Amongseveral 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. 147
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 DIFFICULTIESActually, we face many problems which may affect the development of biosensors. Amongthem we mention the following :- 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 BIOSENSORa. Benefits of integrationThe integration provides many advantages :- 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 haveother criteria such as: compatibility with the integrated electronic circuits (IC’s), the low costand the dimensions. But we will focus on drawbacks as criteria summary of choice and thedegree of integrability which gave us the following table (Table 01):c. Example of an integrated sensor “the Lab.on.Chip” First, let’s start by defining the bio chip. It is a matrix of individual biosensors that can becontrolled individually and often used for the analysis of multiple analytes. 148
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 Major inconvenienes  Degree of integrability Type Calorimetric - Scope to use relatively small for the Low enzymes. Optic -The ambient light often causes - Low for the usual type optical strong interferences. biosensor SPR (Surface Plasmon - The cost of optical fiber is Resonance). expensive. - Good for the Mach Zender - Phase indicators need to be interferometer voice but remains in removed after a while. development. Acoustic (type -Problem of integration (requires Low SAW) several modules instead of one) - Difficulties in using low frequency. - Instability if the temperature varies. Electrochimical -reproducibility: problems for some Very good especially for electronic techniques. microelectronic techniques (Isfet’s, - Average sensitivity often Nernstian TFT, etc.) especially for the PH type. Mass (piezo) - Instability if the temperature varies. Low - Low sensitivity in liquid medium due to the problems of low viscosity.This matrix is integrated into a single box.The Laboratory - on-chip (Figure 05) or "Lab .On. Chip" is a mega bio-chip that integratesmore than the biosensors the complement modules such as bioamplifiers etc. It is amultidisciplinary approach we select and it allows us to minimize energy consumption andincrease the speed of biochemical reactions. In fact it includes all the benefits of integratedcircuits such as the possibility of increased automation and robotics. Fig.4– Circuit board of Lab-on-a-chip  The Lab.On.Chip is used for the study of : ADN, proteins and peptides, cells, antibodies andantigens.It exists in two (02) forms:- CMOS Imaging (optoelectronic technique). 149
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 andmore uses than the second. Fig. 5– Example of a Lab-On- Chip constitution - type CBCM The circuit shown in FIG (05) illustrates the operating principle of CBCM, the capacity canbe found using the following equation:ሺܫௌ − ܫோ ሻ = ݂. ܸ . ∆ܥ …(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 ithas 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 thethermal properties of biological substances. This is another condition in addition to the studyof 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 itstwo forms: hypothermia and hyperthermia (cases of a disease for example). We will have atransport of heat energy which is called thermal conductivity. It directly affects the thermalresistance of the material (see figure6). 150
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 n°6 represents this model : 1 ܾ ܽ+2ߙ݊ܽݐ.ܮ ܴݐℎ = ݈݊ ቂ .ቀ ቁ ቃ …(2) 2.ܭሺܾ−ܽሻ ܽ ܾ+2ߙ݊ܽݐ.ܮ ܵ = ܾ. ܽ ݐ݅ݓℎ ܾ > ܽIf a=b, then: ܮܴݐℎ = …(3) ܽ.ܭሺܽ+2ߙ݊ܽݐ.ܮሻThe data 1 explains the first situation (when b›a) and the data 2 says the second (b=a).- Thermal expansion: the Thermal warming of a biological substance often causes anincrease in the volume called thermal expansion.These two parameters change more rapidly in solid materials, hence the need for additionalthermal study - in addition to the classic study of heat transfer: convection, conduction andradiation- 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. Wehave several levels of integration, we can add for example a system of temperaturecompensation to the biosensor and say that we have an integrated biosensor but it is only aslight integration.From the table n°1 we can ascertain the benefits of microelectronic techniques and deductthat 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 thebiosensors specially. The essential difficulty still resides on the necessity to have a coherentdevelopment in several disciplines (biology, chemical, electronics, software, etc.). So it’s acontinuing multidisciplinary research which is imposed. 151
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), © IAEME8. REFERENCES1 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.jpg3 http://www.astrosurf.com/luxorion/Sciences/loimoore-2010.gif4 Jacob Fraden, “Handbook of modern sensors: physics, designs, and applications”, Editor: Springer, third Edition, p.4, 20045 Gabor Harsanyi, “Sensors in Biomedical Applications- Fundamentals Technology and Applications-”, Editor: CRC- Press, p.226, 2000. Norbert Noury, “Du signal à l’information: le capteur intelligent, Exemples industriels et en médicine”, HDR, Université 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.jpg8 www.chem.agilent.com/cag/feature/8-98/ feature_graphics/chip.jpg9 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. 152
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