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Bio-Techniques in Electrochemical Transducers: an Overview

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Volume 82<br />

Issue 8<br />

August 2007<br />

Sensors & <strong>Tr<strong>an</strong>sducers</strong><br />

www.sensorsportal.com<br />

Editor-<strong>in</strong>-Chief: professor Sergey Y. Yurish, phone: +34 696067716, fax: +34 93 4011989,<br />

e-mail: editor@sensorsportal.com<br />

Editors for Western Europe<br />

Meijer, Gerard C.M., Delft University of Technology, The Netherl<strong>an</strong>ds<br />

Ferrari, Vitorio, Universitá di Brescia, Italy<br />

Editors for North America<br />

Datskos, P<strong>an</strong>os G., Oak Ridge National Laboratory, USA<br />

Fabien, J. Josse, Marquette University, USA<br />

Katz, Evgeny, Clarkson University, USA<br />

Abdul Rahim, Ruzairi, Universiti Teknologi, Malaysia<br />

Ahmad, Mohd Noor, Nothern University of Eng<strong>in</strong>eer<strong>in</strong>g, Malaysia<br />

Annamalai, Karthigey<strong>an</strong>, National Institute of Adv<strong>an</strong>ced Industrial<br />

Science <strong>an</strong>d Technology, Jap<strong>an</strong><br />

Arcega, Fr<strong>an</strong>cisco, University of Zaragoza, Spa<strong>in</strong><br />

Arguel, Philippe, CNRS, Fr<strong>an</strong>ce<br />

Ahn, Jae-Pyoung, Korea Institute of Science <strong>an</strong>d Technology, Korea<br />

Arndt, Michael, Robert Bosch GmbH, Germ<strong>an</strong>y<br />

Ascoli, Giorgio, George Mason University, USA<br />

Atalay, Selcuk, Inonu University, Turkey<br />

Atghiaee, Ahmad, University of Tehr<strong>an</strong>, Ir<strong>an</strong><br />

Augutis, Vyg<strong>an</strong>tas, Kaunas University of Technology, Lithu<strong>an</strong>ia<br />

Avachit, Patil Lalch<strong>an</strong>d, North Maharashtra University, India<br />

Ayesh, Aladd<strong>in</strong>, De Montfort University, UK<br />

Bahreyni, Behraad, University of M<strong>an</strong>itoba, C<strong>an</strong>ada<br />

Baoxi<strong>an</strong>, Ye, Zhengzhou University, Ch<strong>in</strong>a<br />

Barford, Lee, Agilent Laboratories, USA<br />

Barl<strong>in</strong>gay, Rav<strong>in</strong>dra, Priyadarsh<strong>in</strong>i College of Eng<strong>in</strong>eer<strong>in</strong>g <strong>an</strong>d<br />

Architecture, India<br />

Basu, Sukumar, Jadavpur University, India<br />

Beck, Stephen, University of Sheffield, UK<br />

Ben Bouzid, Sihem, Institut National de Recherche Scientifique, Tunisia<br />

B<strong>in</strong>nie, T. David, Napier University, UK<br />

Bischoff, Gerl<strong>in</strong>de, Inst. Analytical Chemistry, Germ<strong>an</strong>y<br />

Bodas, Dh<strong>an</strong><strong>an</strong>jay, IMTEK, Germ<strong>an</strong>y<br />

Borges Carval, Nuno, Universidade de Aveiro, Portugal<br />

Bousbia-Salah, Mounir, University of Annaba, Algeria<br />

Bouvet, Marcel, CNRS – UPMC, Fr<strong>an</strong>ce<br />

Brudzewski, Kazimierz, Warsaw University of Technology, Pol<strong>an</strong>d<br />

Cai, Chenx<strong>in</strong>, N<strong>an</strong>j<strong>in</strong>g Normal University, Ch<strong>in</strong>a<br />

Cai, Q<strong>in</strong>gyun, Hun<strong>an</strong> University, Ch<strong>in</strong>a<br />

Camp<strong>an</strong>ella, Luigi, University La Sapienza, Italy<br />

Carvalho, Vitor, M<strong>in</strong>ho University, Portugal<br />

Cecelja, Fr<strong>an</strong>jo, Brunel University, London, UK<br />

Cerda Belmonte, Judith, Imperial College London, UK<br />

Chakrabarty, Ch<strong>an</strong>d<strong>an</strong> Kumar, Universiti Tenaga Nasional, Malaysia<br />

Chakravorty, Dip<strong>an</strong>kar, Association for the Cultivation of Science, India<br />

Ch<strong>an</strong>ghai, Ru, Harb<strong>in</strong> Eng<strong>in</strong>eer<strong>in</strong>g University, Ch<strong>in</strong>a<br />

Chaudhari, Gaj<strong>an</strong><strong>an</strong>, Shri Shivaji Science College, India<br />

Chen, Rongshun, National Ts<strong>in</strong>g Hua University, Taiw<strong>an</strong><br />

Cheng, Kuo-Sheng, National Cheng Kung University, Taiw<strong>an</strong><br />

Chiriac, Horia, National Institute of Research <strong>an</strong>d Development, Rom<strong>an</strong>ia<br />

Chowdhuri, Arijit, University of Delhi, India<br />

Chung, Wen-Yaw, Chung Yu<strong>an</strong> Christi<strong>an</strong> University, Taiw<strong>an</strong><br />

Corres, Jesus, Universidad Publica de Navarra, Spa<strong>in</strong><br />

Cortes, Camilo A., Universidad de La Salle, Colombia<br />

Courtois, Christi<strong>an</strong>, Universite de Valenciennes, Fr<strong>an</strong>ce<br />

Cus<strong>an</strong>o, Andrea, University of S<strong>an</strong>nio, Italy<br />

D'Amico, Arnaldo, Università di Tor Vergata, Italy<br />

De Stef<strong>an</strong>o, Luca, Institute for Microelectronics <strong>an</strong>d Microsystem, Italy<br />

Deshmukh, Kir<strong>an</strong>, Shri Shivaji Mahavidyalaya, Barshi, India<br />

K<strong>an</strong>g, Moonho, Sunmoon University, Korea South<br />

K<strong>an</strong>iusas, Eugenijus, Vienna University of Technology, Austria<br />

Katake, Anup, Texas A&M University, USA<br />

Editorial Advisory Board<br />

Editor South America<br />

Costa-Felix, Rodrigo, Inmetro, Brazil<br />

ISSN 1726-5479<br />

Editor for Eastern Europe<br />

Sachenko, Anatoly, Ternopil State Economic University, Ukra<strong>in</strong>e<br />

Editor for Asia<br />

Ohyama, Sh<strong>in</strong>ji, Tokyo Institute of Technology, Jap<strong>an</strong><br />

Dickert, Fr<strong>an</strong>z L., Vienna University, Austria<br />

Dieguez, Angel, University of Barcelona, Spa<strong>in</strong><br />

Dimitropoulos, P<strong>an</strong>os, University of Thessaly, Greece<br />

D<strong>in</strong>g Ji<strong>an</strong>, N<strong>in</strong>g, Ji<strong>an</strong>gsu University, Ch<strong>in</strong>a<br />

Djordjevich, Alex<strong>an</strong>dar, City University of Hong Kong, Hong Kong<br />

Donato, Nicola, University of Mess<strong>in</strong>a, Italy<br />

Donato, Patricio, Universidad de Mar del Plata, Argent<strong>in</strong>a<br />

Dong, Feng, Ti<strong>an</strong>j<strong>in</strong> University, Ch<strong>in</strong>a<br />

Drljaca, Predrag, Instersema Sensoric SA, Switzerl<strong>an</strong>d<br />

Dubey, Venketesh, Bournemouth University, UK<br />

Enderle, Stef<strong>an</strong>, University of Ulm <strong>an</strong>d KTB mechatronics GmbH,<br />

Germ<strong>an</strong>y<br />

Erdem, Gurs<strong>an</strong> K. Arzum, Ege University, Turkey<br />

Erkmen, Ayd<strong>an</strong> M., Middle East Technical University, Turkey<br />

Estelle, Patrice, Insa Rennes, Fr<strong>an</strong>ce<br />

Estrada, Horacio, University of North Carol<strong>in</strong>a, USA<br />

Faiz, Adil, INSA Lyon, Fr<strong>an</strong>ce<br />

Ferice<strong>an</strong>, Sor<strong>in</strong>, Balluff GmbH, Germ<strong>an</strong>y<br />

Fern<strong>an</strong>des, Jo<strong>an</strong>a M., University of Porto, Portugal<br />

Fr<strong>an</strong>cioso, Luca, CNR-IMM Institute for Microelectronics <strong>an</strong>d<br />

Microsystems, Italy<br />

Fu, Weil<strong>in</strong>g, South-Western Hospital, Chongq<strong>in</strong>g, Ch<strong>in</strong>a<br />

Gaura, Elena, Coventry University, UK<br />

Geng, Y<strong>an</strong>feng, Ch<strong>in</strong>a University of Petroleum, Ch<strong>in</strong>a<br />

Gole, James, Georgia Institute of Technology, USA<br />

Gong, Hao, National University of S<strong>in</strong>gapore, S<strong>in</strong>gapore<br />

Gonzalez de la Ros, Ju<strong>an</strong> Jose, University of Cadiz, Spa<strong>in</strong><br />

Gr<strong>an</strong>el, Annette, Goteborg University, Sweden<br />

Graff, Mason, The University of Texas at Arl<strong>in</strong>gton, USA<br />

Gu<strong>an</strong>, Sh<strong>an</strong>, Eastm<strong>an</strong> Kodak, USA<br />

Guillet, Bruno, University of Caen, Fr<strong>an</strong>ce<br />

Guo, Zhen, New Jersey Institute of Technology, USA<br />

Gupta, Narendra Kumar, Napier University, UK<br />

Hadjiloucas, Sillas, The University of Read<strong>in</strong>g, UK<br />

Hashsham, Syed, Michig<strong>an</strong> State University, USA<br />

Hern<strong>an</strong>dez, Alvaro, University of Alcala, Spa<strong>in</strong><br />

Hern<strong>an</strong>dez, Wilmar, Universidad Politecnica de Madrid, Spa<strong>in</strong><br />

Homentcovschi, Dorel, SUNY B<strong>in</strong>ghamton, USA<br />

Horstm<strong>an</strong>, Tom, U.S. Automation Group, LLC, USA<br />

Hsiai, Tzung (John), University of Southern California, USA<br />

Hu<strong>an</strong>g, Jeng-Sheng, Chung Yu<strong>an</strong> Christi<strong>an</strong> University, Taiw<strong>an</strong><br />

Hu<strong>an</strong>g, Star, National Ts<strong>in</strong>g Hua University, Taiw<strong>an</strong><br />

Hu<strong>an</strong>g, Wei, PSG Design Center, USA<br />

Hui, David, University of New Orle<strong>an</strong>s, USA<br />

Jaffrezic-Renault, Nicole, Ecole Centrale de Lyon, Fr<strong>an</strong>ce<br />

Jaime Calvo-Galleg, Jaime, Universidad de Salam<strong>an</strong>ca, Spa<strong>in</strong><br />

James, D<strong>an</strong>iel, Griffith University, Australia<br />

J<strong>an</strong>t<strong>in</strong>g, Jakob, DELTA D<strong>an</strong>ish Electronics, Denmark<br />

Ji<strong>an</strong>g, Liudi, University of Southampton, UK<br />

Jiao, Zheng, Sh<strong>an</strong>ghai University, Ch<strong>in</strong>a<br />

John, Joachim, IMEC, Belgium<br />

Kalach, Andrew, Voronezh Institute of M<strong>in</strong>istry of Interior, Russia<br />

Rodriguez, Angel, Universidad Politecnica de Cataluna, Spa<strong>in</strong><br />

Rothberg, Steve, Loughborough University, UK


Kausel, Wilfried, University of Music, Vienna, Austria<br />

Kavasoglu, Nese, Mugla University, Turkey<br />

Ke, Cathy, Tyndall National Institute, Irel<strong>an</strong>d<br />

Kh<strong>an</strong>, Asif, Aligarh Muslim University, Aligarh, India<br />

Kim, M<strong>in</strong> Young, Koh Young Technology, Inc., Korea South<br />

Ko, S<strong>an</strong>g Choon, Electronics <strong>an</strong>d Telecommunications Research Institute,<br />

Korea South<br />

Kockar, Hak<strong>an</strong>, Balikesir University, Turkey<br />

Kotulska, Malgorzata, Wroclaw University of Technology, Pol<strong>an</strong>d<br />

Kratz, Henrik, Uppsala University, Sweden<br />

Kumar, Arun, University of South Florida, USA<br />

Kumar, Subodh, National Physical Laboratory, India<br />

Kung, Chih-Hsien, Ch<strong>an</strong>g-Jung Christi<strong>an</strong> University, Taiw<strong>an</strong><br />

Lacnjevac, Caslav, University of Belgrade, Serbia<br />

Laurent, Fr<strong>an</strong>cis, IMEC , Belgium<br />

Lay-Ekuakille, Aime, University of Lecce, Italy<br />

Lee, J<strong>an</strong>g Myung, Pus<strong>an</strong> National University, Korea South<br />

Lee, Jun Su, Amkor Technology, Inc. South Korea<br />

Li, Genxi, N<strong>an</strong>j<strong>in</strong>g University, Ch<strong>in</strong>a<br />

Li, Hui, Sh<strong>an</strong>ghai Jiaotong University, Ch<strong>in</strong>a<br />

Li, Xi<strong>an</strong>-F<strong>an</strong>g, Central South University, Ch<strong>in</strong>a<br />

Li<strong>an</strong>g, Yu<strong>an</strong>ch<strong>an</strong>g, University of Wash<strong>in</strong>gton, USA<br />

Liawru<strong>an</strong>grath, Saisunee, Chi<strong>an</strong>g Mai University, Thail<strong>an</strong>d<br />

Liew, Kim Meow, City University of Hong Kong, Hong Kong<br />

L<strong>in</strong>, Herm<strong>an</strong>n, National Kaohsiung University, Taiw<strong>an</strong><br />

L<strong>in</strong>, Paul, Clevel<strong>an</strong>d State University, USA<br />

L<strong>in</strong>derholm, Pontus, EPFL - Microsystems Laboratory, Switzerl<strong>an</strong>d<br />

Liu, Aihua, Michig<strong>an</strong> State University, USA<br />

Liu Ch<strong>an</strong>ggeng, Louisi<strong>an</strong>a State University, USA<br />

Liu, Cheng-Hsien, National Ts<strong>in</strong>g Hua University, Taiw<strong>an</strong><br />

Liu, Songq<strong>in</strong>, Southeast University, Ch<strong>in</strong>a<br />

Lodeiro, Carlos, Universidade NOVA de Lisboa, Portugal<br />

Lorenzo, Maria Encarnacio, Universidad Autonoma de Madrid, Spa<strong>in</strong><br />

Lukaszewicz, Jerzy Pawel, Nicholas Copernicus University, Pol<strong>an</strong>d<br />

Ma, Zh<strong>an</strong>f<strong>an</strong>g, Northeast Normal University, Ch<strong>in</strong>a<br />

Majstorovic, Vidosav, University of Belgrade, Serbia<br />

Marquez, Alfredo, Centro de Investigacion en Materiales Av<strong>an</strong>zados,<br />

Mexico<br />

Matay, Ladislav, Slovak Academy of Sciences, Slovakia<br />

Mathur, Prafull, National Physical Laboratory, India<br />

Maurya, D.K., Institute of Materials Research <strong>an</strong>d Eng<strong>in</strong>eer<strong>in</strong>g, S<strong>in</strong>gapore<br />

Mekid, Samir, University of M<strong>an</strong>chester, UK<br />

Mendes, Paulo, University of M<strong>in</strong>ho, Portugal<br />

Mennell, Julie, Northumbria University, UK<br />

Mi, B<strong>in</strong>, Boston Scientific Corporation, USA<br />

M<strong>in</strong>as, Graca, University of M<strong>in</strong>ho, Portugal<br />

Moghavvemi, Mahmoud, University of Malaya, Malaysia<br />

Mohammadi, Mohammad-Reza, University of Cambridge, UK<br />

Mol<strong>in</strong>a Flores, Esteb<strong>an</strong>, Benemirita Universidad Autonoma de Puebla,<br />

Mexico<br />

Moradi, Majid, University of Kerm<strong>an</strong>, Ir<strong>an</strong><br />

Morello, Rosario, DIMET, University "Mediterr<strong>an</strong>ea" of Reggio Calabria,<br />

Italy<br />

Mounir, Ben Ali, University of Sousse, Tunisia<br />

Mukhopadhyay, Subhas, Massey University, New Zeal<strong>an</strong>d<br />

Neelamegam, Periasamy, Sastra Deemed University, India<br />

Neshkova, Milka, Bulgari<strong>an</strong> Academy of Sciences, Bulgaria<br />

Oberhammer, Joachim, Royal Institute of Technology, Sweden<br />

Ould Lahouc<strong>in</strong>, University of Guelma, Algeria<br />

Pamidigh<strong>an</strong>ta, Say<strong>an</strong>u, Bharat Electronics Limited (BEL), India<br />

P<strong>an</strong>, Jisheng, Institute of Materials Research & Eng<strong>in</strong>eer<strong>in</strong>g, S<strong>in</strong>gapore<br />

Park, Joon-Shik, Korea Electronics Technology Institute, Korea South<br />

Pereira, Jose Miguel, Instituto Politecnico de Setebal, Portugal<br />

Petsev, Dimiter, University of New Mexico, USA<br />

Pogacnik, Lea, University of Ljublj<strong>an</strong>a, Slovenia<br />

Post, Michael, National Research Council, C<strong>an</strong>ada<br />

Pr<strong>an</strong>ce, Robert, University of Sussex, UK<br />

Prasad, Ambika, Gulbarga University, India<br />

Prateepasen, Asa, K<strong>in</strong>gmoungut's University of Technology, Thail<strong>an</strong>d<br />

Pull<strong>in</strong>i, D<strong>an</strong>iele, Centro Ricerche FIAT, Italy<br />

Pumera, Mart<strong>in</strong>, National Institute for Materials Science, Jap<strong>an</strong><br />

Radhakrishn<strong>an</strong>, S. National Chemical Laboratory, Pune, India<br />

Raj<strong>an</strong>na, K., Indi<strong>an</strong> Institute of Science, India<br />

Ramad<strong>an</strong>, Qasem, Institute of Microelectronics, S<strong>in</strong>gapore<br />

Rao, Basuthkar, Tata Inst. of Fundamental Research, India<br />

Reig, C<strong>an</strong>did, University of Valencia, Spa<strong>in</strong><br />

Restivo, Maria Teresa, University of Porto, Portugal<br />

Rezazadeh, Ghader, Urmia University, Ir<strong>an</strong><br />

Robert, Michel, University Henri Po<strong>in</strong>care, Fr<strong>an</strong>ce<br />

Royo, S<strong>an</strong>tiago, Universitat Politecnica de Catalunya, Spa<strong>in</strong><br />

Sad<strong>an</strong>a, Ajit, University of Mississippi, USA<br />

S<strong>an</strong>dacci, Serghei, Sensor Technology Ltd., UK<br />

Sapozhnikova, Ksenia, D.I.Mendeleyev Institute for Metrology, Russia<br />

Saxena, Vibha, Bhbha Atomic Research Centre, Mumbai, India<br />

Schneider, John K., Ultra-Sc<strong>an</strong> Corporation, USA<br />

Seif, Selem<strong>an</strong>i, Alabama A & M University, USA<br />

Seifter, Achim, Los Alamos National Laboratory, USA<br />

Sengupta, Deepak, Adv<strong>an</strong>ce <strong>Bio</strong>-Photonics, India<br />

Shearwood, Christopher, N<strong>an</strong>y<strong>an</strong>g Technological University, S<strong>in</strong>gapore<br />

Sh<strong>in</strong>, Kyuho, Samsung Adv<strong>an</strong>ced Institute of Technology, Korea<br />

Shmaliy, Yuriy, Kharkiv National University of Radio Electronics,<br />

Ukra<strong>in</strong>e<br />

Silva Girao, Pedro, Technical University of Lisbon Portugal<br />

Slomovitz, D<strong>an</strong>iel, UTE, Uruguay<br />

Smith, Mart<strong>in</strong>, Open University, UK<br />

Soleym<strong>an</strong>pour, Ahmad, Damgh<strong>an</strong> Basic Science University, Ir<strong>an</strong><br />

Som<strong>an</strong>i, Prakash R., Centre for Materials for Electronics Technology,<br />

India<br />

Sr<strong>in</strong>ivas, Talabattula, Indi<strong>an</strong> Institute of Science, B<strong>an</strong>galore, India<br />

Srivastava, Arv<strong>in</strong>d K., Northwestern University<br />

Stef<strong>an</strong>-v<strong>an</strong> Staden, Raluca-Io<strong>an</strong>a, University of Pretoria, South Africa<br />

Sumriddetchka, Sarun, National Electronics <strong>an</strong>d Computer Technology<br />

Center, Thail<strong>an</strong>d<br />

Sun, Chengli<strong>an</strong>g, Polytechnic University, Hong-Kong<br />

Sun, Dongm<strong>in</strong>g, Jil<strong>in</strong> University, Ch<strong>in</strong>a<br />

Sun, Junhua, Beij<strong>in</strong>g University of Aeronautics <strong>an</strong>d Astronautics, Ch<strong>in</strong>a<br />

Sun, Zhiqi<strong>an</strong>g, Central South University, Ch<strong>in</strong>a<br />

Suri, C. Ram<strong>an</strong>, Institute of Microbial Technology, India<br />

Sysoev, Victor, Saratov State Technical University, Russia<br />

Szewczyk, Rom<strong>an</strong>, Industrial Research Institute for Automation <strong>an</strong>d<br />

Measurement, Pol<strong>an</strong>d<br />

T<strong>an</strong>, Ooi Ki<strong>an</strong>g, N<strong>an</strong>y<strong>an</strong>g Technological University, S<strong>in</strong>gapore,<br />

T<strong>an</strong>g, Di<strong>an</strong>p<strong>in</strong>g, Southwest University, Ch<strong>in</strong>a<br />

T<strong>an</strong>g, Jaw-Luen, National Chung Cheng University, Taiw<strong>an</strong><br />

Thumbav<strong>an</strong>am Pad, Kartik, Carnegie Mellon University, USA<br />

Tsi<strong>an</strong>tos, Vassilios, Technological Educational Institute of Kaval, Greece<br />

Tsigara, Anna, National Hellenic Research Foundation, Greece<br />

Twomey, Karen, University College Cork, Irel<strong>an</strong>d<br />

Valente, Antonio, University, Vila Real, - U.T.A.D., Portugal<br />

Vaseashta, Ashok, Marshall University, USA<br />

Vazques, Carmen, Carlos III University <strong>in</strong> Madrid, Spa<strong>in</strong><br />

Vieira, M<strong>an</strong>uela, Instituto Superior de Engenharia de Lisboa, Portugal<br />

Vigna, Benedetto, STMicroelectronics, Italy<br />

Vrba, Radimir, Brno University of Technology, Czech Republic<br />

W<strong>an</strong>delt, Barbara, Technical University of Lodz, Pol<strong>an</strong>d<br />

W<strong>an</strong>g, Ji<strong>an</strong>gp<strong>in</strong>g, Xi'<strong>an</strong> Shiyou University, Ch<strong>in</strong>a<br />

W<strong>an</strong>g, Kedong, Beih<strong>an</strong>g University, Ch<strong>in</strong>a<br />

W<strong>an</strong>g, Li<strong>an</strong>g, Adv<strong>an</strong>ced Micro Devices, USA<br />

W<strong>an</strong>g, Mi, University of Leeds, UK<br />

W<strong>an</strong>g, Sh<strong>in</strong>n-Fwu, Ch<strong>in</strong>g Yun University, Taiw<strong>an</strong><br />

W<strong>an</strong>g, Wei-Chih, University of Wash<strong>in</strong>gton, USA<br />

W<strong>an</strong>g, Wensheng, University of Pennsylv<strong>an</strong>ia, USA<br />

Watson, Steven, Center for N<strong>an</strong>oSpace Technologies Inc., USA<br />

Weip<strong>in</strong>g, Y<strong>an</strong>, Dali<strong>an</strong> University of Technology, Ch<strong>in</strong>a<br />

Wells, Stephen, Southern Comp<strong>an</strong>y Services, USA<br />

Wolkenberg, Andrzej, Institute of Electron Technology, Pol<strong>an</strong>d<br />

Woods, R. Clive, Louisi<strong>an</strong>a State University, USA<br />

Wu, DerHo, National P<strong>in</strong>gtung University of Science <strong>an</strong>d Technology,<br />

Taiw<strong>an</strong><br />

Wu, Zhaoy<strong>an</strong>g, Hun<strong>an</strong> University, Ch<strong>in</strong>a<br />

Xiu Tao, Ge, Chuzhou University, Ch<strong>in</strong>a<br />

Xu, Tao, University of California, Irv<strong>in</strong>e, USA<br />

Y<strong>an</strong>g, Dongf<strong>an</strong>g, National Research Council, C<strong>an</strong>ada<br />

Y<strong>an</strong>g, Wuqi<strong>an</strong>g, The University of M<strong>an</strong>chester, UK<br />

Ymeti, Aurel, University of Twente, Netherl<strong>an</strong>d<br />

Yu, Haihu, Wuh<strong>an</strong> University of Technology, Ch<strong>in</strong>a<br />

Yufera Garcia, Alberto, Seville University, Spa<strong>in</strong><br />

Zagnoni, Michele, University of Southampton, UK<br />

Zeni, Luigi, Second University of Naples, Italy<br />

Zhong, Haoxi<strong>an</strong>g, Hen<strong>an</strong> Normal University, Ch<strong>in</strong>a<br />

Zh<strong>an</strong>g, M<strong>in</strong>glong, Sh<strong>an</strong>ghai University, Ch<strong>in</strong>a<br />

Zh<strong>an</strong>g, Q<strong>in</strong>tao, University of California at Berkeley, USA<br />

Zh<strong>an</strong>g, Weip<strong>in</strong>g, Sh<strong>an</strong>ghai Jiao Tong University, Ch<strong>in</strong>a<br />

Zh<strong>an</strong>g, Wenm<strong>in</strong>g, Sh<strong>an</strong>ghai Jiao Tong University, Ch<strong>in</strong>a<br />

Zhou, Zhi-G<strong>an</strong>g, Ts<strong>in</strong>ghua University, Ch<strong>in</strong>a<br />

Zorz<strong>an</strong>o, Luis, Universidad de La Rioja, Spa<strong>in</strong><br />

Zourob, Mohammed, University of Cambridge, UK<br />

Sensors & <strong>Tr<strong>an</strong>sducers</strong> Journal (ISSN 1726-5479) is a peer review <strong>in</strong>ternational journal published monthly onl<strong>in</strong>e by International Frequency Sensor Association (IFSA).<br />

Available <strong>in</strong> electronic <strong>an</strong>d CD-ROM. Copyright © 2007 by International Frequency Sensor Association. All rights reserved.


Volume 82<br />

Issue 8<br />

August 2007<br />

Research Articles<br />

Sensors & <strong>Tr<strong>an</strong>sducers</strong> Journal<br />

Contents<br />

www.sensorsportal.com<br />

ISSN 1726-5479<br />

Sensor Signal Condition<strong>in</strong>g<br />

David Cheeke .................................................................................................................................... 1381<br />

Sensor Interfaces for Private Home Automation: From Analog to Digital, Wireless <strong>an</strong>d<br />

Autonomous<br />

E. Leder, A. Sutor, M. Meiler, R. Lerch, B. Pulvermueller, M. Guenther............................................ 1389<br />

<strong>Bio</strong>-<strong>Techniques</strong> <strong>in</strong> <strong>Electrochemical</strong> <strong>Tr<strong>an</strong>sducers</strong>: <strong>an</strong> <strong>Overview</strong><br />

Vikas & C. S. Pundir ........................................................................................................................... 1405<br />

Design of a Novel Capacitive Pressure Sensor<br />

Ebrahim Abbaspour-S<strong>an</strong>i, Sodabeh Soleim<strong>an</strong>i .................................................................................. 1418<br />

A Ppb Formaldehyde Gas Sensor for Fast Indoor Air Quality Measurements<br />

Hélène Paolacci, R. Dagnelie, D. Porterat, Fr<strong>an</strong>çois Piuzzi, Fabien Lepetit, Thu-Hoa Tr<strong>an</strong>-Thi....... 1423<br />

Model<strong>in</strong>g <strong>an</strong>d Analysis of Fiber Optic R<strong>in</strong>g Resonator Perform<strong>an</strong>ce as Temperature Sensor<br />

S<strong>an</strong>joy M<strong>an</strong>dal, S.K.Ghosh, T.K.Basak.............................................................................................. 1431<br />

An Optoelectronic Sensor Configuration Us<strong>in</strong>g ZnO Thick Film for Detection of Meth<strong>an</strong>ol<br />

Shobhna Dixit, K. P. Misra, Atul Srivastava, Anchal Srivastava <strong>an</strong>d R. K. Shukla............................. 1443<br />

Enh<strong>an</strong>ced Acoustic Sensitivity <strong>in</strong> Polymeric Coated Fiber Bragg Grat<strong>in</strong>g<br />

A. Cus<strong>an</strong>o, S. D’Addio, A. Cutolo, S. Campopi<strong>an</strong>o, M. Balbi, S. Balzar<strong>in</strong>i, M. Giord<strong>an</strong>o................... 1450<br />

Lactase from Clarias Gariep<strong>in</strong>us <strong>an</strong>d its Application <strong>in</strong> Development of Lactose Sensor<br />

S<strong>an</strong>deep K. Sharma, Neeta Sehgal <strong>an</strong>d Ashok Kumar ..................................................................... 1458<br />

Prism Based Real Time Refractometer<br />

Anchal Srivastava, R. K. Shukla, Atul Srivastava,M<strong>an</strong>oj K. Srivastava <strong>an</strong>d Dharmendra Mishra ..... 1470<br />

Development of a micro-SPM (Sc<strong>an</strong>n<strong>in</strong>g Probe Microscope) by post-assembly of a MEMSstage<br />

<strong>an</strong>d <strong>an</strong> <strong>in</strong>dependent c<strong>an</strong>tilever<br />

Zhi Li, Helmut Wolff, Konrad Herrm<strong>an</strong>n ............................................................................................. 1480<br />

Design, Packag<strong>in</strong>g <strong>an</strong>d Characterization of a L<strong>an</strong>gasite Monolithic Crystal Filter Viscometer<br />

J. Andle, R. Haskell, R. Sbardella, G. Morehead, M. Chap, S. Xiong,J. Columbus, D. Stevens, <strong>an</strong>d<br />

K. Durdag............................................................................................................................................ 1486<br />

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International Frequency Sensor Association (IFSA).


Sensors & <strong>Tr<strong>an</strong>sducers</strong> Journal, Vol.82, Issue 8, August 2007, pp. 1405-1417<br />

Sensors & <strong>Tr<strong>an</strong>sducers</strong><br />

ISSN 1726-5479<br />

© 2007 by IFSA<br />

http://www.sensorsportal.com<br />

<strong>Bio</strong>-<strong>Techniques</strong> <strong>in</strong> <strong>Electrochemical</strong> <strong>Tr<strong>an</strong>sducers</strong>: <strong>an</strong> <strong>Overview</strong><br />

VIKAS & C. S. PUNDIR<br />

Department of <strong>Bio</strong>chemistry & Genetics, Maharishi Day<strong>an</strong><strong>an</strong>d University,<br />

Rohtak-124001, India<br />

Tel.: 00 91 09254160010<br />

E-mail: biosensor_tech@yahoo.com<br />

Received: 2 June 2007 /Accepted: 20 August 2007 /Published: 27 August 2007<br />

Abstract: Novelty <strong>in</strong> fabrication & design<strong>in</strong>g of biosensors are be<strong>in</strong>g carried out at a high rate as these<br />

devices become <strong>in</strong>creas<strong>in</strong>gly popular <strong>in</strong> fields like environmental monitor<strong>in</strong>g, bioterrorism, food<br />

<strong>an</strong>alyses <strong>an</strong>d most import<strong>an</strong>tly <strong>in</strong> the area of health care <strong>an</strong>d diagnostics. This rapidly exp<strong>an</strong>d<strong>in</strong>g field<br />

has <strong>an</strong> <strong>an</strong>nual growth rate of 65%, with major impetus from the health-care <strong>in</strong>dustry (30% of the<br />

world’s total <strong>an</strong>alytical market) supported with other <strong>an</strong>alytical areas of food & environmental<br />

monitor<strong>in</strong>g <strong>in</strong>clud<strong>in</strong>g defense needs. This context aims to highlight trends <strong>in</strong> practice for<br />

electrochemical biosensor design <strong>an</strong>d construction. The availability <strong>an</strong>d application of a vast r<strong>an</strong>ge of<br />

polymers <strong>an</strong>d copolymers associated with new sens<strong>in</strong>g techniques have led to remarkable <strong>in</strong>novation<br />

<strong>in</strong> the design <strong>an</strong>d construction of biosensors, signific<strong>an</strong>t improvements <strong>in</strong> sensor function <strong>an</strong>d the<br />

emergence of new types of biosensor. Nevertheless, <strong>in</strong> vivo applications rema<strong>in</strong> limited by functional<br />

deterioration due to surface foul<strong>in</strong>g by biological components. However, use of new material <strong>an</strong>d<br />

novelty <strong>in</strong> fabrication, rais<strong>in</strong>g hopes that the problems related to decreased functional of the<br />

bio<strong>an</strong>alytical layer be solved <strong>in</strong> time. Copyright © 2007 IFSA.<br />

Keywords: <strong>Bio</strong>sensor, Electrode, <strong>Electrochemical</strong>, Immobilization, Fabrication<br />

1. Introduction<br />

Most recently, biosensors as versatile <strong>an</strong>alytical tools have been <strong>in</strong>creas<strong>in</strong>gly used for cont<strong>in</strong>uous<br />

monitor<strong>in</strong>g of vial biochemical parameters <strong>in</strong> body fluids <strong>an</strong>d to atta<strong>in</strong> the <strong>an</strong>alytical <strong>in</strong>formation <strong>in</strong> a<br />

faster m<strong>an</strong>ner. Potential applications cont<strong>in</strong>ued to lie <strong>in</strong> cl<strong>in</strong>ical diagnostics, bioprocess, environmental<br />

monitor<strong>in</strong>g <strong>an</strong>d food <strong>an</strong>d drug <strong>in</strong>dustries. <strong>Bio</strong>sensors c<strong>an</strong> also meet the need for cont<strong>in</strong>uous, real-time<br />

<strong>in</strong> vivo monitor<strong>in</strong>g to replace the <strong>in</strong>termittent <strong>an</strong>alytical techniques used <strong>in</strong> <strong>in</strong>dustrial <strong>an</strong>d cl<strong>in</strong>ical<br />

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chemistry [1]. As low cost, portable, <strong>an</strong>d simple-to-operate <strong>an</strong>alytical tool, biosensors have hade<br />

certa<strong>in</strong> adv<strong>an</strong>tages over he conventional <strong>an</strong>alytical <strong>in</strong>struments such as gas chromatographs. The<br />

systematic description of a biosensor should <strong>in</strong>clude five features [2]. These are (1) the detected or<br />

measured parameter, (2) the work<strong>in</strong>g pr<strong>in</strong>ciple of the tr<strong>an</strong>sducer, (3) the physical <strong>an</strong>d chemical:<br />

biochemical model, (4) the application <strong>an</strong>d (5) the technology <strong>an</strong>d materials for sensor fabrication.<br />

M<strong>an</strong>y parameters have been suggested to characterize biosensors. Some are commonly used to<br />

evaluate the functional properties <strong>an</strong>d quality of the sensor, such as sensitivity, stability <strong>an</strong>d response<br />

time; while other parameters are related to the application rather th<strong>an</strong> to sensor function, for example<br />

the biocompatibility of sensors for cl<strong>in</strong>ical monitor<strong>in</strong>g. The first blood pO2 electrode was <strong>in</strong>troduced<br />

by Clark [3]. He described how to make electrochemical sensors more <strong>in</strong>telligent by add<strong>in</strong>g "enzyme<br />

tr<strong>an</strong>sducers as membr<strong>an</strong>e enclosed s<strong>an</strong>dwiches”. This idea was commercially exploited <strong>in</strong> 1975 with<br />

the successful launch of the Yellow Spr<strong>in</strong>gs Instrument Comp<strong>an</strong>y’s glucose <strong>an</strong>alyzer based on the<br />

amperometric detection of hydrogen peroxide (H2O2) [4]. S<strong>in</strong>ce then, m<strong>an</strong>y biosensors have been<br />

developed to detect a wide r<strong>an</strong>ge of biochemical parameters, us<strong>in</strong>g a number of approaches, each<br />

hav<strong>in</strong>g a different degree of complexity <strong>an</strong>d efficiency. <strong>Bio</strong>sensors <strong>in</strong>corporat<strong>in</strong>g enzymes have been<br />

developed to measure concentrations of carbohydrates (glucose, galactose <strong>an</strong>d fructose), prote<strong>in</strong>s<br />

(cholesterol <strong>an</strong>d creat<strong>in</strong><strong>in</strong>e), am<strong>in</strong>o acids (glutamate) <strong>an</strong>d metabolites (lactate, urea <strong>an</strong>d oxalate<br />

oxidase) <strong>in</strong> blood <strong>an</strong>d other body fluids <strong>an</strong>d tissues. It is even possible to measure the concentrations of<br />

neurotr<strong>an</strong>smitter molecules by me<strong>an</strong>s of a neuronal biosensor <strong>an</strong>d the application of this technique is<br />

also studied <strong>in</strong> the actions of <strong>an</strong>esthetics [5-6]. A r<strong>an</strong>ge of biologically active molecules, <strong>in</strong>clud<strong>in</strong>g<br />

<strong>an</strong>tibodies <strong>an</strong>d <strong>an</strong>tigens has also been measured us<strong>in</strong>g immuno-sensors [7]. Recently, the most<br />

fasc<strong>in</strong>at<strong>in</strong>g <strong>an</strong>d prospective sensors <strong>in</strong>cludes biosensors for the detection of DNA damage <strong>an</strong>d<br />

mutation [8-9], <strong>an</strong>d the identification of DNA sequences <strong>an</strong>d hybridization [10] offers considerable<br />

promise <strong>in</strong> several medical fields. The reaction between the bioactive subst<strong>an</strong>ce <strong>an</strong>d the species<br />

(substrate) produces a product <strong>in</strong> the form of a biological or chemical subst<strong>an</strong>ce, heat, light, or sound;<br />

then the tr<strong>an</strong>sducer such as <strong>an</strong> electrode, semiconductor, thermistor, photocounter, or sound detector<br />

ch<strong>an</strong>ges the product of the reaction <strong>in</strong>to usable data. Therefore, depend<strong>in</strong>g on the technique used<br />

tr<strong>an</strong>sducers c<strong>an</strong> be subdivided <strong>in</strong>to the follow<strong>in</strong>g four ma<strong>in</strong> types.<br />

1. <strong>Electrochemical</strong> <strong>Tr<strong>an</strong>sducers</strong>: (a) Potentiometric: These <strong>in</strong>volve the measurement of the emf<br />

(potential) of a cell at zero current. The emf is proportional to the logarithm of the concentration of the<br />

subst<strong>an</strong>ce be<strong>in</strong>g determ<strong>in</strong>ed. (b) Voltammetric: An <strong>in</strong>creas<strong>in</strong>g (decreas<strong>in</strong>g) potential is applied to the<br />

cell until oxidation (reduction) of the subst<strong>an</strong>ce to be <strong>an</strong>alyzed occurs <strong>an</strong>d there is a sharp rise (fall) <strong>in</strong><br />

the current to give a peak current. The height of the peak current is directly proportional to the<br />

concentration of the electroactive material. If the appropriate oxidation (reduction) potential is known,<br />

one may step the potential directly to that value <strong>an</strong>d observe the current. This mode is known as<br />

amperometric (c) Conductometric: Most reactions <strong>in</strong>volve a ch<strong>an</strong>ge <strong>in</strong> the composition of the solution.<br />

This will normally result <strong>in</strong> a ch<strong>an</strong>ge <strong>in</strong> the electrical conductivity of the solution, which c<strong>an</strong> be<br />

measured electrically.(d) FET-based sensors: M<strong>in</strong>iaturization c<strong>an</strong> sometimes be achieved by<br />

construct<strong>in</strong>g one of the above types of electrochemical tr<strong>an</strong>sducers on a silicon chip-based field-effect<br />

tr<strong>an</strong>sistor. This method has ma<strong>in</strong>ly been used with potentiometric sensors, but could also be used with<br />

voltammetric or conductometric sensors.<br />

2. Optical <strong>Tr<strong>an</strong>sducers</strong>: These have taken a new lease of life with the development of fibre optics, thus<br />

allow<strong>in</strong>g greater flexibility <strong>an</strong>d m<strong>in</strong>iaturization. The techniques used <strong>in</strong>clude absorption spectroscopy,<br />

fluorescence spectroscopy, <strong>an</strong>d lum<strong>in</strong>escence spectroscopy, <strong>in</strong>ternal reflection spectroscopy, surface<br />

plasmon spectroscopy <strong>an</strong>d light scatter<strong>in</strong>g.<br />

3. Piezo-electric Devices: These devices <strong>in</strong>volve the generation of electric currents from a vibrat<strong>in</strong>g<br />

crystal. The frequency of vibration is affected by the mass of material adsorbed on its surface, which<br />

could be related to ch<strong>an</strong>ges <strong>in</strong> a reaction. Surface acoustic wave devices are a related system.<br />

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4. Thermal Sensors: All chemical <strong>an</strong>d biochemical processes <strong>in</strong>volve the production or absorption of<br />

heat. This heat c<strong>an</strong> be measured by sensitive thermistors <strong>an</strong>d hence be related to the amount of<br />

subst<strong>an</strong>ce to be <strong>an</strong>alyzed.<br />

The selectivity of the biosensor for the target <strong>an</strong>alyte is ma<strong>in</strong>ly determ<strong>in</strong>ed by the biorecognition<br />

element, while the sensitivity of biosensor is greatly <strong>in</strong>fluenced by the tr<strong>an</strong>sducer. Most cl<strong>in</strong>ical<br />

applications have, so far, been restricted to academic studies <strong>an</strong>d research laboratories rather th<strong>an</strong><br />

commercialized for rout<strong>in</strong>e cl<strong>in</strong>ical monitor<strong>in</strong>g. The pr<strong>in</strong>cipal reason for this limitation is the poor<br />

biocompatibility of available materials which <strong>in</strong>terferes with sensor function [11]. The selection of<br />

materials <strong>an</strong>d fabrication techniques is crucial for adequate sensor function <strong>an</strong>d the perform<strong>an</strong>ce of a<br />

biosensor often ultimately depends upon these factors rather th<strong>an</strong> upon the other factors mentioned<br />

above.<br />

2. Materials<br />

Materials used <strong>in</strong> electrochemical biosensors are classified as: (1) electrodes types <strong>an</strong>d support<strong>in</strong>g<br />

substrates, (2) materials used for the immobilization of biological elements (3), membr<strong>an</strong>e materials<br />

<strong>an</strong>d biocompatibility <strong>an</strong>d (4), biological recognition elements such as enzymes, <strong>an</strong>tibodies, <strong>an</strong>tigens,<br />

nucleic acids, mediators <strong>an</strong>d cofactors.<br />

2.1. Electrodes Types <strong>an</strong>d Support<strong>in</strong>g Substrates<br />

Metals <strong>an</strong>d carbon are commonly used to prepare solid electrode systems <strong>an</strong>d support<strong>in</strong>g substrates.<br />

Metals such as plat<strong>in</strong>um, gold, silver <strong>an</strong>d sta<strong>in</strong>less steel have long been used for electrochemical<br />

electrodes due to their excellent electrical <strong>an</strong>d mech<strong>an</strong>ical properties. Carbon-based materials such as<br />

graphite, carbon black <strong>an</strong>d carbon fiber are also used to construct the conductive phase. These<br />

materials have a high chemical <strong>in</strong>ertness <strong>an</strong>d provide a wide r<strong>an</strong>ge of <strong>an</strong>ode work<strong>in</strong>g potentials with<br />

low electrical resistivity. They also have a very pure crystal structure that provides low residual<br />

currents <strong>an</strong>d a high signal-to-noise ratio [12]. Carbon fibers could be valuable <strong>in</strong> sensor construction<br />

<strong>an</strong>d he showed how a parallel array consist<strong>in</strong>g of a large number of carbon fibres, separated by<br />

<strong>in</strong>sulators, c<strong>an</strong> be prepared to obta<strong>in</strong> a very high signal-to-noise ratio [13]. More recently, a number of<br />

new mixed materials have appeared for the preparation of electrodes. A conduct<strong>in</strong>g composite formed<br />

by the comb<strong>in</strong>ation of two, or more, dissimilar materials was <strong>in</strong>troduced by [12]. Each material reta<strong>in</strong>s<br />

its orig<strong>in</strong>al properties, while giv<strong>in</strong>g the composite dist<strong>in</strong>ct chemical, mech<strong>an</strong>ical <strong>an</strong>d physical<br />

properties that differ from those exhibited by the <strong>in</strong>dividual components. A carbon-polymer based<br />

composite is firstly prepared by dispers<strong>in</strong>g powdered graphite <strong>in</strong> a polymer res<strong>in</strong>, such as epoxy,<br />

silicone, methacrylate, polyester or polyureth<strong>an</strong>e. With the biological recognition element previously<br />

immobilized onto carbon particles, modifier, catalyst or mediator, the polymer composite is then<br />

mixed to form the <strong>in</strong>tegrated electrode unit. Us<strong>in</strong>g this method, <strong>an</strong> impure metal work<strong>in</strong>g electrode was<br />

prepared with the catalyst <strong>an</strong>d enzyme adsorbed onto pyrolysedcobalt–tetramethoxy–phenylporphyr<strong>in</strong>(CoTM<br />

PP) [14]. From this basic pressed matrix tablet, it is possible to m<strong>an</strong>ufacture<br />

numerous electrodes with identical functional properties <strong>in</strong> terms of sensitivity, l<strong>in</strong>earity <strong>an</strong>d lifetime.<br />

Org<strong>an</strong>ic electro conductive polymers have aroused considerable <strong>in</strong>terest <strong>in</strong> recent years. These<br />

materials c<strong>an</strong> be used to prepare electrodes, or to provide a substrate for the immobilization of<br />

biological elements (see next section) simult<strong>an</strong>eously. A novel electrode was fabricated by the use of a<br />

flexible conductive polymer film of polypyrrole doped with poly <strong>an</strong>ions <strong>an</strong>d a microporous layer of<br />

plat<strong>in</strong>um black [15]. Glucose sensors produced with this material provided a H2O2 oxidation current at<br />

a lower applied potential th<strong>an</strong> conventional sensors.<br />

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2.2. Materials Used for the Immobilization of <strong>Bio</strong>logical Elements<br />

Most of the materials traditionally used for this purpose are multifunctional agents such as<br />

glutaraldehyde <strong>an</strong>d hexamethyl diisocy<strong>an</strong>ate, which form crossl<strong>in</strong>ks between biocatalytic species, or<br />

prote<strong>in</strong>s. The process is known as coreticulation, s<strong>in</strong>ce it creates complex matrices that make multi<br />

enzyme immobilization possible. Alternatively, non-conductive polymers, such as polyacrylamide <strong>an</strong>d<br />

polyphenol, c<strong>an</strong> be used to entrap elements physically. Org<strong>an</strong>ic conductive polymers provide<br />

adv<strong>an</strong>tages, <strong>in</strong>clud<strong>in</strong>g the formation of <strong>an</strong> appropriate environment for enzyme immobilization at the<br />

electrode <strong>an</strong>d for its <strong>in</strong>teraction with metallic <strong>an</strong>d carbon conductors [16-17]. Therefore, electrical<br />

communication between the redox centre <strong>an</strong>d the electrode surface is more efficient. These polymers<br />

c<strong>an</strong> be deposited electrolytically from solution onto a conduct<strong>in</strong>g support to provide a three<br />

dimensional matrix for immobilized enzymes where react<strong>an</strong>ts are converted to products. The polymers<br />

c<strong>an</strong> be produced by a variety of chemical processes, <strong>in</strong>clud<strong>in</strong>g the Ziegler–Natta reaction for<br />

polyacetylene [18-19], the creation of <strong>an</strong> electrolyte solution e.g. poly (p-phenylene) [20], the coupl<strong>in</strong>g<br />

of org<strong>an</strong>ometallic components (polythiophene) [21] <strong>an</strong>d the oxidation of monomers [22]. Redox<br />

polymer hydrogels entrap oxidoreductases efficiently <strong>an</strong>d tr<strong>an</strong>sfer electrons from enzymatic oxidation:<br />

reduction reactions through the gel to the conduct<strong>in</strong>g surface [23]. Gels based on networks of<br />

polyethylene glycol, diacrylate <strong>an</strong>d v<strong>in</strong>ylferrocene c<strong>an</strong> be formed by illum<strong>in</strong>at<strong>in</strong>g a solution conta<strong>in</strong><strong>in</strong>g<br />

the comonomers <strong>an</strong>d the ultraviolet photo<strong>in</strong>itiator,2,2%-dimethoxy-2-phenylacetophenone at 365 nm,<br />

20 W cm_2. The enzyme c<strong>an</strong> then be loaded by dissolv<strong>in</strong>g it <strong>in</strong> this mixture followed by exposure to<br />

light. Latex particles also provide suitable substrates for the controlled attachment of biomolecules <strong>in</strong><br />

the recognition of <strong>an</strong>alytes. Studies on the formation of two-dimensional latex assemblies covalently<br />

immobilized on conduct<strong>in</strong>g solid surfaces were performed [24]. Computer simulations illustrated the<br />

general properties of the 2-D latex assemblies <strong>an</strong>d a real example of the composite, polystyrene:<br />

acrole<strong>in</strong>latex, on a quartz surface were presented.<br />

2.3. Membr<strong>an</strong>e Materials <strong>an</strong>d <strong>Bio</strong>compatibility<br />

<strong>Bio</strong>sensors are usually covered with a th<strong>in</strong> membr<strong>an</strong>e that has several functions, <strong>in</strong>clud<strong>in</strong>g diffusion<br />

control, reduction of <strong>in</strong>terference <strong>an</strong>d mech<strong>an</strong>ical protection of the sens<strong>in</strong>g probe. Commercially<br />

available polymers, such as polyv<strong>in</strong>yl chloride (PVC), polyethylene, polymethacrylate <strong>an</strong>d<br />

polyureth<strong>an</strong>e are commonly used for the preparation of these membr<strong>an</strong>es due to their suitable physical<br />

<strong>an</strong>d chemical properties. <strong>Bio</strong>sensors with polymer membr<strong>an</strong>es have been successfully applied <strong>in</strong> m<strong>an</strong>y<br />

fields such as the monitor<strong>in</strong>g of food production, environmental pollution <strong>an</strong>d pathological specimens.<br />

However, when biosensors are placed <strong>in</strong> a biological environment, numerous factors operate to affect<br />

their perform<strong>an</strong>ce, the most signific<strong>an</strong>t ones be<strong>in</strong>g sensor surface <strong>in</strong>teractions with prote<strong>in</strong>s <strong>an</strong>d cells<br />

[25]. Therefore, although biosensors have great potential for real-time cl<strong>in</strong>ical monitor<strong>in</strong>g, the sensors<br />

so far constructed lack functional stability after impl<strong>an</strong>tation <strong>an</strong>d sensor lifetime is usually restricted to<br />

several hours, or days [26]. Thus, functional stability is profoundly affected by the biocompatibility of<br />

the biosensor materials that are <strong>in</strong> contact with the biological medium. Attempts to improve the<br />

biocompatibility of artificial surfaces by bond<strong>in</strong>g <strong>an</strong>ticoagul<strong>an</strong>ts have not been very successful. For<br />

example, the surface treatment of membr<strong>an</strong>es with hepar<strong>in</strong> sulphate is commonly used to improve<br />

haemocompatibility, but when Smith <strong>an</strong>d Sefton (1993) <strong>an</strong>alyzed thromb<strong>in</strong> adsorption onto hepar<strong>in</strong><br />

treated polyv<strong>in</strong>yl alcohol <strong>an</strong>d polyureth<strong>an</strong>e, they observed that, whereas the rate of adsorption of<br />

thromb<strong>in</strong> was reduced by hepar<strong>in</strong> coat<strong>in</strong>g, the f<strong>in</strong>al volume of thromb<strong>in</strong> desorbed rema<strong>in</strong>ed similar<br />

[27]. Another problem is that the hepar<strong>in</strong> tends to leach from the membr<strong>an</strong>e surface <strong>in</strong>to the<br />

surround<strong>in</strong>g medium. Materials with hydrogel-like properties are generally considered to favor<br />

biocompatibility. Water associates with the water-soluble polymers <strong>an</strong>d the presence of water around<br />

the polymer h<strong>in</strong>ders prote<strong>in</strong> adsorption due to the energetically unfavorable displacement of water by<br />

prote<strong>in</strong> <strong>an</strong>d compression of the polymer upon the approach of prote<strong>in</strong>. These factors have been<br />

described <strong>in</strong> terms of steric repulsion, v<strong>an</strong> der Waals attraction, <strong>an</strong>d hydrophobic <strong>in</strong>teractive free<br />

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energies [28-29] by Jeon et al. (1991) <strong>an</strong>d by Jeon <strong>an</strong>d Andrade (1991). Surfaces grafted with watersoluble<br />

polymers have been developed us<strong>in</strong>g a number of techniques, <strong>in</strong>clud<strong>in</strong>g end-graft<strong>in</strong>g [30]<br />

(Shoichet et al., 1994) <strong>an</strong>d <strong>in</strong> situ polymerization by photo- or wet- chemistry, <strong>an</strong>d by radio frequency<br />

glow discharge deposition [31] An alternative to surface graft<strong>in</strong>g is the adsorption of amphiphilic<br />

molecules onto hydrophobic polymers. Amphiphatic molecules c<strong>an</strong> rearr<strong>an</strong>ge themselves on a surface<br />

<strong>in</strong> <strong>an</strong> attempt to maximize pack<strong>in</strong>g density <strong>an</strong>d c<strong>an</strong> be covalently immobilized on the surface to create<br />

a perm<strong>an</strong>ent adsorption layer [32]. Polyethylene glycol (PEG) has been used extensively to modify<br />

surfaces, so that prote<strong>in</strong> adsorption <strong>an</strong>d platelet <strong>in</strong>teractions with the foreign surface are reduced [33].<br />

The natural cell membr<strong>an</strong>e is a self-assembled system <strong>an</strong>d the extra-cellular matrix is a n<strong>an</strong>o-structured<br />

system. Based upon these observations, amphiphilic, self assembled multilayers <strong>an</strong>d n<strong>an</strong>o-structured<br />

surface systems have been exploited <strong>in</strong> the production of liposomes modified with PEG. These<br />

surfaces suffer from signific<strong>an</strong>tly less prote<strong>in</strong> adsorption <strong>an</strong>d immune clear<strong>an</strong>ce mech<strong>an</strong>isms are<br />

reduced [34]. Chemical adsorption has been used to produce self-assembled monolayers on metals <strong>an</strong>d<br />

ceramics. Alk<strong>an</strong>es term<strong>in</strong>ated with thiols form densely packed monolayers, with the alk<strong>an</strong>e cha<strong>in</strong><br />

oriented outwardly from the substrate surface. It is reported that prote<strong>in</strong> adsorption could be virtually<br />

elim<strong>in</strong>ated by alk<strong>an</strong>e thiol term<strong>in</strong>ated with oligoethylene glycol [35]. An optical biosensor chemically<br />

adsorbed with a monolayer of 16-mercaptohexadec<strong>an</strong>-1-ol has been produced to measure prote<strong>in</strong><br />

<strong>in</strong>teractions with gold coated surfaces [36].<br />

Surface modification of polymers has led to modest improvements <strong>in</strong> biocompatibility, but it is still not<br />

satisfactory for long-term <strong>in</strong> vivo applications, so there is <strong>an</strong> urgent need to design <strong>an</strong>d develop new<br />

biocompatible materials. Dur<strong>in</strong>g the last two decades, several attempts have been made to do this by<br />

synthesiz<strong>in</strong>g new phospholipid copolymers based upon the pr<strong>in</strong>ciple of biological membr<strong>an</strong>e mimicry.<br />

These copolymers have been successfully used as drug carriers as well as biosensor membr<strong>an</strong>es. The<br />

basic philosophy beh<strong>in</strong>d this idea is due to Zwaal et al., (1977), who described the complex<br />

relationships between cell membr<strong>an</strong>e structure <strong>an</strong>d blood coagulation [37]. In vitro coagulation tests<br />

demonstrated that the <strong>in</strong>ner surfaces of the plasma membr<strong>an</strong>e of erythrocytes <strong>an</strong>d platelets are highly<br />

procoagul<strong>an</strong>t, but the outer surfaces are <strong>in</strong>active. Liposomes hav<strong>in</strong>g the same phospholipid<br />

composition as the outer surfaces of erythrocyte <strong>an</strong>d platelet membr<strong>an</strong>es were also <strong>in</strong>active <strong>an</strong>d did not<br />

reduce the time for recalcified plasma to clot. The simplest common feature of these non-reactive<br />

cellular <strong>an</strong>d model membr<strong>an</strong>es is the high content of electrically neutral phospholipids with<br />

phosphorylchol<strong>in</strong>e head groups [38]. Consequently, the synthetic copolymer, poly (MPC-co-BMA)<br />

which conta<strong>in</strong>s head groups of 2-methacryloyloxyethyl phosphorylchol<strong>in</strong>e (MPC) copolymerised with<br />

n-butylmethacrylate (BMA), also exhibits surface properties that are favourable for<br />

haemocompatibility. The surfaces are extremely hydrophilic <strong>an</strong>d they conta<strong>in</strong> large volumes of water<br />

[39]. Dur<strong>in</strong>g the construction of the membr<strong>an</strong>e by liquid evaporation, the whole phospholipid<br />

molecule, which <strong>in</strong>cludes two fatty acid cha<strong>in</strong>s, undergoes signific<strong>an</strong>t rotation to m<strong>in</strong>imize <strong>in</strong>terface<br />

energy <strong>an</strong>d this result <strong>in</strong> the orientation of the phosphorylchol<strong>in</strong>e head group towards the side of the<br />

membr<strong>an</strong>e that is exposed to air. The MPC moiety also has a strong aff<strong>in</strong>ity for natural phospholipids<br />

molecules <strong>in</strong> plasma, so a well org<strong>an</strong>ized natural lipid layer, biomembr<strong>an</strong>e-like structure, forms on this<br />

surface dur<strong>in</strong>g its exposure to plasma [40]. Prote<strong>in</strong> adsorption is signific<strong>an</strong>tly reduced on poly (MPCco-BMA)<br />

surfaces compared with other medical polymers [41] <strong>an</strong>d the <strong>in</strong> vitro <strong>an</strong>d <strong>in</strong> vivo<br />

perform<strong>an</strong>ce of biosensors is signific<strong>an</strong>tly improved when poly(MPC-co-BMA) is coated onto the<br />

sensor surface [42-44]. These membr<strong>an</strong>es might simulate natural membr<strong>an</strong>es functionally as well as<br />

structurally the natural phospholipids may be cont<strong>in</strong>uously replenished <strong>in</strong> a cont<strong>in</strong>uous process of<br />

erosion <strong>an</strong>d repair [45].<br />

2.4. <strong>Bio</strong>logical Recognition Elements<br />

Improvements <strong>in</strong> <strong>in</strong>terface design have frequently been directed at the <strong>in</strong>corporation of active<br />

molecules, <strong>in</strong>clud<strong>in</strong>g enzymes such as glucose oxidase [4] <strong>an</strong>d lactate oxidase [46], mediators, such as<br />

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Ferrocene (h2-bis-cyclopentadienyliron) <strong>an</strong>d its derivatives [47], cofactors based on nicot<strong>in</strong>amide<br />

aden<strong>in</strong>e d<strong>in</strong>ucleotide(NADH_ <strong>an</strong>d NADP_ [48], catalysts [49], <strong>an</strong>tibodies <strong>an</strong>d <strong>an</strong>tigens [50]. Studies<br />

on the use of biosensors for gene detection are relatively recent <strong>an</strong>d still uncommon.<br />

Deoxyribonucleicacid (DNA) has recently been suggested as a biological recognition element for such<br />

biosensors [51-52]. The unique nucleotide base structure of DNA provides the basis of the technique<br />

which allows s<strong>in</strong>gle str<strong>an</strong>ded DNA (ssDNA) to be used to identify other ssDNA molecules with the<br />

complementary bases [53]. Therefore, nucleic acid hybridisation is the underly<strong>in</strong>g operat<strong>in</strong>g pr<strong>in</strong>ciple<br />

of DNA biosensors. Dur<strong>in</strong>g the last decade, there have been m<strong>an</strong>y adv<strong>an</strong>ces <strong>in</strong> DNA biosensor<br />

technology <strong>an</strong>d most work has focused on electrochemical, piezoelectric <strong>an</strong>d optical tr<strong>an</strong>sducers.<br />

Attempts to develop <strong>an</strong> electrochemical DNA biosensor have been made by several groups [54-55]. In<br />

these sensors, <strong>an</strong> ssDNA str<strong>an</strong>d is covalently bound to the surface of <strong>an</strong> electrode. Hybridization of the<br />

immobilized sequence with its dissolved complement forms the double str<strong>an</strong>d that c<strong>an</strong> be detected<br />

us<strong>in</strong>g a DNA-specific redox-active metal: polypyrid<strong>in</strong>e complex. Damaged segments of DNA c<strong>an</strong> also<br />

be detected by measur<strong>in</strong>g ch<strong>an</strong>ges <strong>in</strong> the redox signals of base residues <strong>in</strong> DNA immobilized on carbon<br />

electrodes. Covalently closed circular DNA c<strong>an</strong> be attached to <strong>an</strong> electrode surface to obta<strong>in</strong> a sensor<br />

that detects a s<strong>in</strong>gle break <strong>in</strong> the DNA sugar-phosphate backbone, or for the detection of agents<br />

leav<strong>in</strong>g the DNA backbone such as hydroxyl radicals, ioniz<strong>in</strong>g radiation or nucleases [56].DNA<br />

sens<strong>in</strong>g protocols, based on different modes of nucleic acid <strong>in</strong>teraction have been reviewed [57] by<br />

W<strong>an</strong>g et al. (1997). The review describes recent efforts to couple nucleic acid recognition layers to<br />

electrochemical tr<strong>an</strong>sducers. Peptide nucleic acids (PNAs) have been found to exhibit unique <strong>an</strong>d<br />

efficient hybridization properties that may offer signific<strong>an</strong>t adv<strong>an</strong>tages for sequence-specific<br />

recognition compared to their DNA counterparts. The adv<strong>an</strong>tages <strong>in</strong>clude higher sensitivity <strong>an</strong>d<br />

specificity, faster hybridization at room temperature <strong>an</strong>d m<strong>in</strong>imal dependence upon ionic strength. The<br />

use of PNA <strong>in</strong>corporated with a Co (phen) (3) (3+) redox <strong>in</strong>dicator on a carbon electrode for the<br />

detection of sequence specific DNA has been discussed [58].<br />

3. Design<strong>in</strong>g of <strong>Bio</strong>sensors<br />

Design <strong>an</strong>d construction technology <strong>an</strong>d material science are <strong>in</strong>timately l<strong>in</strong>ked <strong>in</strong> biosensor<br />

development. Therefore, discussions of biosensor design <strong>an</strong>d fabrication should always <strong>in</strong>volve the<br />

selection of materials. An electrochemical biosensor usually consists of a tr<strong>an</strong>sducer such as a pair of<br />

electrodes or FET, <strong>an</strong> <strong>in</strong>terface layer <strong>in</strong>corporat<strong>in</strong>g the biological recognition molecules <strong>an</strong>d a<br />

protective coat<strong>in</strong>g. Sensor design, <strong>in</strong>clud<strong>in</strong>g materials, size <strong>an</strong>d shape <strong>an</strong>d methods of construction, are<br />

largely dependent upon the pr<strong>in</strong>ciple of operation of the tr<strong>an</strong>sducer, the parameters to be detected <strong>an</strong>d<br />

the work<strong>in</strong>g environment. Traditional electrode systems for measurements of the concentrations of<br />

ions <strong>in</strong> liquids <strong>an</strong>d dissolved gas partial pressures conta<strong>in</strong> only a work<strong>in</strong>g electrode (usually a noble<br />

metal wire) <strong>an</strong>d <strong>an</strong> electrically stable reference electrode, such as Ag: AgCl, though a counter<br />

electrode is sometimes <strong>in</strong>cluded. A simple electrical, or chemical, modification may sometimes<br />

improve specific electrode properties. For example, repeated potential cycl<strong>in</strong>g of 0.3 mm diameter<br />

carbon rods <strong>in</strong> 0.1 M potassium hexacy<strong>an</strong> ferrate improved the stability of glucose sensors for up to<br />

6.5 days [59]. However, with the exp<strong>an</strong>d<strong>in</strong>g dem<strong>an</strong>ds for more complex measurements, the rapid<br />

development of materials science <strong>an</strong>d the emergence of micro- <strong>an</strong>d n<strong>an</strong>oprocess technology, <strong>in</strong>direct<br />

electrochemical methods <strong>in</strong> simple biosensors to monitor enzyme activity have gradually been<br />

replaced by more direct, but more complex processes. Methods for the preparation of electrochemical<br />

electrodes are well established. Some of these techniques are used to prepare the conductive<br />

support<strong>in</strong>g substrate, while others are employed to achieve <strong>an</strong> efficient electrical communication<br />

between the chemical reaction site <strong>an</strong>d the electrode surface, high levels of <strong>in</strong>tegration, sensor<br />

m<strong>in</strong>iaturization, measurement stability, selectivity, accuracy <strong>an</strong>d precision. In addition, the technique<br />

used to immobilize the biological recognition components of the sensor c<strong>an</strong> affect biosensor<br />

perform<strong>an</strong>ce signific<strong>an</strong>tly.<br />

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3.1. Tr<strong>an</strong>sducer/Electrode Fabrication<br />

The electrode support<strong>in</strong>g substrate c<strong>an</strong> be a noble metal (gold or plat<strong>in</strong>um), carbon rod or paste, or <strong>an</strong><br />

org<strong>an</strong>ic conduct<strong>in</strong>g salt or polymer. <strong>Techniques</strong> used for the production of conductive support<strong>in</strong>g<br />

substrates c<strong>an</strong> be roughly classified as: (1) pr<strong>in</strong>t<strong>in</strong>g, (2) deposition, (3) polymerization, (4) plasma<br />

<strong>in</strong>duced polymerization, (5) photolithography <strong>an</strong>d (6) n<strong>an</strong>o-technology.<br />

(1) Screen-pr<strong>in</strong>t<strong>in</strong>g is one of the thick-film techniques that have been widely used <strong>in</strong> <strong>in</strong>dustry for mass<br />

production. Paste material is pr<strong>in</strong>ted onto a matrix directly through a mask-net with a designed pattern.<br />

The technique of carbon, or graphite, screen pr<strong>in</strong>t<strong>in</strong>g is now frequently used to prepare electrodes for<br />

biosensors. Turner’s group recently improved this technique by us<strong>in</strong>g solvent resist<strong>an</strong>t materials; heat<br />

stabilized polyester sheet, carbon base tracks <strong>an</strong>d <strong>an</strong> epoxy-based polymer [60]. These electrodes have<br />

no problems with solvent <strong>in</strong>duced basel<strong>in</strong>e shift <strong>an</strong>d are therefore suitable for work <strong>in</strong> water-miscible<br />

org<strong>an</strong>ic solvents. Sensor arrays for the detection of more th<strong>an</strong> one parameter by different sens<strong>in</strong>g<br />

techniques, or to assemble a package of sensors to measure the same parameter, have potential<br />

practical applications. For this purpose, the screen pr<strong>in</strong>t<strong>in</strong>g technique has been used to prepare a sevench<strong>an</strong>nel<br />

electrode for simult<strong>an</strong>eous amperometric <strong>an</strong>d potentiometric measurements. The array<br />

conta<strong>in</strong>s 14 gold work<strong>in</strong>g <strong>an</strong>d counter electrodes <strong>an</strong>d one Ag: AgCl reference electrode [61]. This<br />

sensor c<strong>an</strong> be used to <strong>an</strong>alyse blood <strong>an</strong>d serum electrolytes <strong>an</strong>d metabolites. A pr<strong>in</strong>table paste is<br />

prepared by mix<strong>in</strong>g glucose oxidase adsorbed org<strong>an</strong>ic charge tr<strong>an</strong>sfer complex crystals with a b<strong>in</strong>der<br />

<strong>an</strong>d a solvent [62]. This paste is pr<strong>in</strong>ted onto a matrix cavity <strong>an</strong>d dried under vacuum. A th<strong>in</strong> layer of<br />

gelat<strong>in</strong> is then cast on the electrode. The developed sensor provides a huge response current with<br />

m<strong>in</strong>imum <strong>in</strong>terference from oxygen <strong>an</strong>d <strong>an</strong> extended l<strong>in</strong>ear r<strong>an</strong>ge up to 100 mM glucose. <strong>Techniques</strong><br />

(2), (3), (4) <strong>an</strong>d (5) are thick-th<strong>in</strong>-film techniques that are used <strong>in</strong> biosensors to form mono or multilayers<br />

of conduct<strong>in</strong>g film onto a support<strong>in</strong>g substrate <strong>in</strong> order to obta<strong>in</strong> a direct electrical<br />

communication between the chemical: biochemical reaction site <strong>an</strong>d the support<strong>in</strong>g surface. Factors<br />

affect<strong>in</strong>g electron tr<strong>an</strong>sfer from biological molecules to electrode surface have also been reviewed<br />

[63].<br />

(2) Traditional chemical, or electrochemical, deposition methods c<strong>an</strong> be used to deposit <strong>an</strong> electro<br />

conductive film on a support<strong>in</strong>g substrate. The deposited film c<strong>an</strong> be metal such as plat<strong>in</strong>um, catalytic<br />

material such as TiO, or a metal complex. <strong>Bio</strong>logical elements c<strong>an</strong> also be simult<strong>an</strong>eously coupled<br />

dur<strong>in</strong>g the film deposition process. Lorenzo et al. (1998) discussed the <strong>an</strong>alytical strategies for various<br />

electrodeposited films [64].<br />

(3) Polymerisation takes place due to the condensation of small molecules <strong>in</strong> monomers, or by free<br />

radical creation <strong>an</strong>d reaction by rearr<strong>an</strong>g<strong>in</strong>g the bonds with <strong>in</strong> each monomer. Free radicals are<br />

produced when the double bond is broken by <strong>in</strong>itiation activated by heat, light, or electro-chemicals.<br />

Electrical conductivity c<strong>an</strong> be achieved by the <strong>in</strong>troduction of metal powder <strong>in</strong>to the monomer before<br />

polymerization, or through electrons that are not conjugated <strong>in</strong> the monomer. A new technique has<br />

been developed to generate polymethylene blue-modified thick-film on gold electrodes by<br />

electropolymerisation to form <strong>an</strong> eletrocatalytically active conduct<strong>in</strong>g layer that is <strong>in</strong> <strong>in</strong>timate <strong>an</strong>d<br />

stable contact with the electrode surface. This process allows for a reduced applied potential of only<br />

200 mV, the avoid<strong>an</strong>ce of <strong>in</strong>ference from co-oxidisable species <strong>an</strong>d the m<strong>in</strong>imization of electrode<br />

foul<strong>in</strong>g [65]. By deposit<strong>in</strong>g a th<strong>in</strong> electropolymerised film of poly(1,3-diam<strong>in</strong>obenzene),<br />

electrochemical <strong>in</strong>terference from ascorbate, urate, acetam<strong>in</strong>ophen <strong>an</strong>d other oxdisable species c<strong>an</strong> be<br />

greatly dim<strong>in</strong>ished. It was reported that a photo-<strong>in</strong>itiated free-radical polymerised redox<br />

hydrogelpolymer entrapped enzymes efficiently [66] <strong>an</strong>d <strong>in</strong>creased the tr<strong>an</strong>sfer of electrons from<br />

enzyme oxidation:reduction reactions through the gel to the electrode surface [23].<br />

(4) Plasma-<strong>in</strong>duced polymerization is performed under high vacuum. The pr<strong>in</strong>ciple is to <strong>in</strong>troduce<br />

functional groups onto the substrate surface <strong>an</strong>d then ‘polymerisable’ gas plasma is coated onto this<br />

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surface to form a layer of film. Plasma-polymerised film, generated <strong>in</strong> a glow discharge, or plasma <strong>in</strong> a<br />

vapor phase, may offer a new alternative for biosensor <strong>in</strong>terface design. The adv<strong>an</strong>tage of this<br />

technique is that it c<strong>an</strong> produce <strong>an</strong> extremely th<strong>in</strong> (B1 mm) film that adheres firmly to substrates.<br />

Furthermore, the film is p<strong>in</strong>-hole free <strong>an</strong>d both mech<strong>an</strong>ically <strong>an</strong>d chemically stable, <strong>an</strong>d it allows a<br />

large amount of biological material to be loaded onto the surface [67].<br />

(5) Photolithography techniques have long been used <strong>in</strong> the semiconductor <strong>in</strong>dustry to produce<br />

<strong>in</strong>tegrated chips. Light passes through a photo-mask <strong>an</strong>d is cast upon a photo degraded material surface<br />

to form a pattern. This technique was used to fabricate micro-lens arrays for sensors [68]. The<br />

m<strong>an</strong>ufacture of <strong>in</strong>tegrate tr<strong>an</strong>sducer arrays for measurements of a s<strong>in</strong>gle parameter, or for several<br />

different parameters, is now possible by me<strong>an</strong>s of photolithography <strong>an</strong>d plasma technology. These<br />

techniques have been used to <strong>in</strong>crease the dynamic r<strong>an</strong>ge <strong>an</strong>d sensitivity of urea sensors [69].<br />

(6) N<strong>an</strong>o-techniques have recently appeared with the maturation of modern technologies such as<br />

surface probe microscopy <strong>an</strong>d lithography, atomic force microscopy (AFM), AFM lithography <strong>an</strong>d<br />

lateral force microscopy (LFM). A brief historical overview, <strong>in</strong> which recent developments <strong>in</strong><br />

m<strong>in</strong>iaturisation, microfabrication, n<strong>an</strong>otechnology, immuno-sensors <strong>an</strong>d gene-sensors are, discussed<br />

[70]. Patterns were produced with resolutions <strong>in</strong> the n<strong>an</strong>ometer r<strong>an</strong>ge based upon photo- <strong>an</strong>d AFM-<br />

lithography with <strong>an</strong> orgaosil<strong>an</strong>e monolayer resists [71].<br />

The comb<strong>in</strong>ation of techniques mentioned above leads to multilayer structures that may well prove to<br />

be useful <strong>in</strong> the development of new types of biosensor. Bilayer polymer coat<strong>in</strong>gs consist<strong>in</strong>g of<br />

polypyrrole acid poly (o-phenylenediam<strong>in</strong>e) on a support<strong>in</strong>g substrate may improve selectivity <strong>an</strong>d<br />

reduced <strong>in</strong>ference from electroactive species like uric <strong>an</strong>d ascorbic acids that areoften present <strong>in</strong><br />

biological samples [72] proposed a multilayer architecture to predef<strong>in</strong>e electron-tr<strong>an</strong>sfer pathways,<br />

<strong>in</strong>tegrate redox mediators, immobilise enzymes <strong>an</strong>d restrict diffusional access by <strong>in</strong>terfer<strong>in</strong>g<br />

compounds [73]. A multilayer wafer c<strong>an</strong> also be formed by deposit<strong>in</strong>g a th<strong>in</strong> functionalized<br />

polypyrrole film on the support<strong>in</strong>g surface <strong>an</strong>d then covalently bond<strong>in</strong>g a redox dye of polymerized<br />

qu<strong>in</strong>oidic species to prevent electrode foul<strong>in</strong>g. The top of this layer is coated with polypyrrole with<br />

entrapped tyro<strong>in</strong>ase. Electrons tr<strong>an</strong>sfer from the qu<strong>in</strong>one to the electrode surface via the immobilized<br />

redox dye. Other new techniques have been suggested that could be useful <strong>in</strong> the design <strong>an</strong>d<br />

construction of new biosensors. The most promis<strong>in</strong>g of these may be the formation of a direct<br />

electrochemical communication between the active enzyme site <strong>an</strong>d the electrode surface us<strong>in</strong>g a<br />

biocatalyst with a very low molecular weight, such as microperoxidase MP-11, immobilised on a thiomonolayer.<br />

In this case, the dist<strong>an</strong>ce between enzyme <strong>an</strong>d electrode surface is greatly reduced <strong>in</strong><br />

comparison with earlier constructions <strong>an</strong>d this modification signific<strong>an</strong>tly <strong>in</strong>creases the strength of the<br />

output signal [74]. Kh<strong>an</strong> (1996b) reported a stable org<strong>an</strong>ic charge-tr<strong>an</strong>sfer-complex (CTC) electrode<br />

for the direct oxidation of flavoprote<strong>in</strong>s [75]. To construct the CTC electrode, tetrathiafulvalenetetracy<strong>an</strong>oqu<strong>in</strong>odimeth<strong>an</strong>e<br />

is grown at the surface of <strong>an</strong> electro conductive poly<strong>an</strong>ion-opedpolypyrrole<br />

film <strong>in</strong> such a way that it makes a tree shaped crystal structure, st<strong>an</strong>d<strong>in</strong>g vertically on the surface. By<br />

immobiliz<strong>in</strong>g a glucose enzyme on the CTC electrode, direct electron tr<strong>an</strong>sfer is achieved between the<br />

active enzyme <strong>an</strong>d the crystal electrode <strong>an</strong>d this leads to remarkably improved sensor perform<strong>an</strong>ce. An<br />

electrically conductive <strong>an</strong>d mech<strong>an</strong>ically flexible composite polymer was prepared to construct a<br />

glucose sensor [76]. Us<strong>in</strong>g this technique, f<strong>in</strong>e palladium particles are dispersed <strong>in</strong> polypyrrole:sulfated<br />

poly(beta-hydroxyethers) by thermally decompos<strong>in</strong>g the bis(dibenzylideneacetone)–palladium<br />

complex. With Ag:AgCl as a reference electrode, a conventional plat<strong>in</strong>um electrode responded to<br />

glucose at a work<strong>in</strong>g potential of 650 mV, whereas the new electrode responded at 400 mV.<br />

Fibr<strong>in</strong>ogen film were used to provide a porous, non-reactive layer over a carbon paste electrode to<br />

control the mass tr<strong>an</strong>sfer rate of diffus<strong>in</strong>g species [77] <strong>an</strong>d the technique of pulsed LASER deposition<br />

(PLD) was <strong>in</strong>troduced with optimized LASER parameters <strong>an</strong>d reaction atmosphere to obta<strong>in</strong> more<br />

efficient enzyme activities th<strong>an</strong> the conventional plat<strong>in</strong>um film electrode produced by argon sputter<strong>in</strong>g<br />

[78].<br />

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Considerable progress has been made <strong>in</strong> the development of new methods of immobiliz<strong>in</strong>g biological<br />

recognition elements onto sensor surfaces. The use of self-assembled mono- <strong>an</strong>d multi-layers (SAMs)<br />

is <strong>in</strong>creas<strong>in</strong>g rapidly <strong>in</strong> various fields of research, <strong>an</strong>d this applies especially to the construction of<br />

biosensors. SAMs c<strong>an</strong> be used as <strong>in</strong>terface layers upon which almost all types of biological<br />

components, <strong>in</strong>clud<strong>in</strong>g prote<strong>in</strong>s, enzymes, <strong>an</strong>tibodies <strong>an</strong>d their receptors, <strong>an</strong>d even nucleotides for<br />

DNA recognition, c<strong>an</strong> be loaded [79]. The use of biomembr<strong>an</strong>es as recognition elements was<br />

<strong>in</strong>troduced by the pioneer<strong>in</strong>g work [80]. Lipid membr<strong>an</strong>es provide are relatively biocompatible surface<br />

<strong>an</strong>d mass diffusion based sensors constructed with lipid membr<strong>an</strong>es hav<strong>in</strong>g fast response rates <strong>an</strong>d<br />

high sensitivities. However, there was no practical use of lipid films until the development of<br />

physically stable bilayer lipid membr<strong>an</strong>es (BLMs). BLMs c<strong>an</strong> be formed on metal surfaces, conductive<br />

polymer supports, or agar plates. The technique usually proceeds by two steps. First, the support<br />

substrate is coated with the lipid layer by immers<strong>in</strong>g it <strong>in</strong> a lipid solution <strong>an</strong>d then placed <strong>in</strong> <strong>an</strong><br />

electrolyte solution to create the self-assembled lipid bilayer. The <strong>in</strong>corporation of biological<br />

recognition molecules <strong>in</strong>to lipid layers <strong>an</strong>d their immobilisation on BLMs depend upon the degree of<br />

access to reactive sites on the molecules. The various techniques used for this purpose have been<br />

described [81]. The technique used to construct <strong>an</strong> immuno-sensor based on a self-assembled BLM<br />

supported on a metal surface was described [82]. Avid<strong>in</strong> modified monoclonal <strong>an</strong>tibodies, orig<strong>in</strong>at<strong>in</strong>g<br />

from the E2:G2 clone (AMab), <strong>an</strong>d matched <strong>an</strong>tigens were <strong>in</strong>corporated <strong>in</strong> the membr<strong>an</strong>e.<br />

Amperometric biosensors for glucose <strong>an</strong>d urea measurement have also been produced by the<br />

immobilization of glucose oxidase <strong>an</strong>d urease <strong>in</strong>to BLMs through the avid<strong>in</strong>–biot<strong>in</strong> <strong>in</strong>teraction [83]. A<br />

layer-by-layer deposition technique may be used to optimize enzyme load<strong>in</strong>g <strong>in</strong> bienzyme systems<br />

[84]. With up to ten monomolecular layers conta<strong>in</strong><strong>in</strong>g avid<strong>in</strong>, biot<strong>in</strong> residues <strong>an</strong>d chol<strong>in</strong>e oxidase<br />

(ChOx), <strong>an</strong>d two superficial layers conta<strong>in</strong><strong>in</strong>g chol<strong>in</strong>eesterase, the sensor exhibits <strong>an</strong> <strong>in</strong>creased<br />

response to acetylchol<strong>in</strong>e. A technique to prepare gold electrodes with n<strong>an</strong>ometersized open<strong>in</strong>gs for<br />

the immobilization of biological recognition elements, such as <strong>an</strong>tibodies, has been described [85].<br />

Latex spheres are used as a mask<strong>in</strong>g material to create 60 nm diameter holes <strong>in</strong> gold film evaporated<br />

onto a support<strong>in</strong>g substrate. The n<strong>an</strong>ometer-scale proximity of the recognition components to the<br />

conduct<strong>in</strong>g surface may facilitate the development of biosensors without mediators. A multi-enzyme<br />

s<strong>an</strong>dwich comprised of layers of separately immobilised enzymes was prepared [86]. Factors<br />

controll<strong>in</strong>g the concentration of enzyme, enzyme k<strong>in</strong>etics, <strong>an</strong>d the permeability <strong>an</strong>d thickness of the<br />

coat<strong>in</strong>g components had been evaluated previously. Enzyme multilayer composed of avid<strong>in</strong>, biot<strong>in</strong>labelled<br />

glucose oxidase <strong>an</strong>d ascorbate oxidase are considered to be resist<strong>an</strong>t to ascorbate <strong>in</strong>terference<br />

[87]. By the use of avid<strong>in</strong> to crossl<strong>in</strong>k <strong>an</strong>d immobilize the glucose oxidase, <strong>an</strong> electro reduction current<br />

may be measured at the extremely low potential of 100 mV [88].<br />

4. Conclusion <strong>an</strong>d Future Prospects<br />

Technology adv<strong>an</strong>ces are enabl<strong>in</strong>g new procedures <strong>in</strong> hospitals while <strong>in</strong>creas<strong>in</strong>g the possibilities for<br />

self-care. For the biosensor to be of optimal use, it must be at least as precise <strong>an</strong>d st<strong>an</strong>dardized as other<br />

available technology. Reduc<strong>in</strong>g blood specimen volumes to micro (µ) level may permit cont<strong>in</strong>uous onl<strong>in</strong>e<br />

monitor<strong>in</strong>g of critical blood chemistries <strong>an</strong>d has the adv<strong>an</strong>tage of creat<strong>in</strong>g less blood to cle<strong>an</strong> up<br />

hence reduc<strong>in</strong>g the potential for <strong>in</strong>fectious contam<strong>in</strong>ation from patient blood. In addition, a s<strong>in</strong>gle chip<br />

<strong>in</strong>sert may measure multiple parameters. Mass production of disposable biosensors will make medical<br />

diagnosis cheaper. Despite huge market potential & except for few commercial successes, m<strong>an</strong>y of the<br />

prototypes of biosensors <strong>in</strong> our laboratories are not commercially viable. The gap between research<br />

<strong>an</strong>d the market place still rema<strong>in</strong>s wide <strong>an</strong>d commercialization of biosensor technology has cont<strong>in</strong>ued<br />

to lag beh<strong>in</strong>d the research by several years. Some of the m<strong>an</strong>y reasons <strong>in</strong>cludes: cost considerations,<br />

stability <strong>an</strong>d sensitivity issues, quality assur<strong>an</strong>ce <strong>an</strong>d competitive technologies. Until all these issues<br />

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are addressed it would be difficult to move these devices from the research lab to market place. In<br />

addition, partial <strong>in</strong>dustrial participation must be encouraged so as to reduce the complexity <strong>in</strong><br />

tr<strong>an</strong>sferr<strong>in</strong>g of prototype or modern technological <strong>in</strong>novation <strong>in</strong>to market place.<br />

Acknowledgment<br />

<strong>Bio</strong>sensor research work <strong>in</strong> author’s lab is funded by Department of <strong>Bio</strong>technology (DBT) <strong>an</strong>d<br />

Department of Science & Technology (DST), New Delhi, India.<br />

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