From Neural Networks and Biomolecular Engineering to Bioelectronics ELECTRONICS AND BIOTECHNOLOGY ADVANCED (EL.B.A.) FORUM SERIES Volume 1 FROM NEURAL NETWORKS AND BIOMOLECULAR ENGINEERING TO BIOELECTRONICS Edited by Claudio Nicolini A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. From Neural Networks and Biomolecular Engineering to Bioelectronics Edited by Claudio Nicolini Institute of Biophysics University of Genoa Genoa, Italy Assistant Editor Sergei Vakula EL.B.A. Foundation Portoferraio, Italy Springer Science+ Business Media, LLC Library of Congress Cataloging-in-Publication Data On file Proceedings of the 1993 International Workshop on Electronics and Biotechnology Advanced, held July 13-16, 1993, on the Isle of Elba, Italy ISBN 978-1-4899-1090-5 ISBN 978-1-4899-1088-2 (eBook) DOI 10.1007/978-1-4899-1088-2 © Springer Science+Business Media New York 1995 Originally published by Plenum Press, New York in 1995 Softcover reprint of the hardcover 1st edition 1995 10 98765432 1 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE This volume represents the fIrst of a series of proceedings of the EL.B.A. Forum on Bioelectronics, a scientifIc discipline at the frontiers of Advanced Electronics and Biotechnology. The name for these forums derives not only from the place (the Isle of Elba in Italy), where the conferences have been held every 6 months since 1991, but also from an acronym: Electronics and Biotechnology Advanced. Bioelectronics is intended as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level" and focuses its attention on three major areas: I New hardware architectures borrowed from the thorough study of brain and sensory systems down to the molecular level, utilizing existing semiconductor inorganic materials (both GaAs and Si) and giga-scale integration; II Protein Engineering, especially of systems involved in electron transfer and molecular recognition, integrated with Metabolism and Chemical Engineering, to develop new biomaterials by learning basic rules of macromolecular folding and self-assembly; m Sensors, thin film and electronic devices utilizing organic compounds and biopolymers, and by implementing nanotechnology bottom up through manufacturing and characterization at the atomic level. Bioelectronics, at the interface of biotechnology and electronics, has been characterized by the Italian Government, as early as 1989, as one of the fIelds of strategic importance for scientifIc and technological research and for potential industrial development. The decision, made in 1989 by the Italian Government, was revolutionary in this fIeld in that for the fIrst time in a National Program of Research scientifIc activity was combined with training-by-research of young scientists. For the fIrst time, provisions were made for an eight-year plan divided into two periods, one of three and the subsequent of fIve years duration. As a result, in 1990 several companies (SGS Thomson, Pharmacia-Farmitalia Carlo Erba, Elsag Bailey, Sorin Biomedica-FIAT, ENICHEM) and an industrial consortium (Technobiochip, recently transformed in a new company operating in the fIeld of Bioelectronics, and a major sponsor of the EL.B.A. Forum), all leaders in their fIelds at the international level, became involved in the research activity sponsored by the National Program of Research "Technologies for Bioelectronics," under the general cover of CIREF. Extremely signifIcant was the formation, in 1990, of Polo Nazionale Bioelettronica, a consortium with headquarters in the Isle of Elba, that is comprised of several leading universities (Genoa, Pisa, Siena, Naples, Catania), national research institutions (ENEA, INBB, National Institute of Health), industrial consortia TECHNOBIOCHIP, CIREF), and fInancial holding companies (Raggio di Sole Biotecnologie, IRI-SPI). One of the milestones in the development of the international cooperation in the fields relevant for bioelectronics was set up by the signing of an international agreement between v Italy and Russia in December 1990. This agreement, signed by Italian Minister Ruberti and Russian Vice-Minister Bortnik, for cooperation in the fields of Biomolecular Engineering and Bioelectronics, resulted in the "Elba Project" between the Russian Academy of Sciences and Polo Nazionale Bioelettronica. As the result of this project a foundation has been established recently involving Polo Nazionale Bioelettronica, the Italian Ministry of Foreign Affairs, the Italian Ministry of University and Scientific and Technological Research, the Russian Ministry of Science and Technical Policy, leading research institutions from Italy, Russia, and the United States, with the participation of the Commission of European Union as an observer. More recently, the same island and acronym (Electronics and Biotechnology Advanced), have given the name to a Scientific and Technological Park, which is becoming a key location of an expanding scientific and technological project of European dimensions focused on Bioelectronics. I would like to express my gratitude particularly to Dr. Sergey Vakula. I would also like to acknowledge the precious assistance of Drs. Paolo Occhialini and Pietro Ragni of AF FORUM, and Dr. Isabella Zolfino of TECHNOBIOCHIP. Thanks are also due to the Ministry of University and Scientific and Technological Research of Italy, which financed this workshop. Claudio Nicolini Member of the National Science and Technology Council March 1, 1994 vi INTRODUCTION The EL.B.A. Forum Series is intended as a series of proceedings of periodic workshops, held on the Isle of Elba, jointly organized by Technobiochip, CIREF, and Polo Nazionale Bioelettronica, starting in 1992. The first forums were held during 1992-1993 at Marciana, with numerous leading scientists participating in these meetings. This series of conferences is intended to give a unique retrospective of what is currently being defined as "bioelectronics." Bioelectronics emerged several years ago at the interface of life and physical sciences and is gaining more and more attention and respect worldwide. Strong evidence of this fact is the interest expressed recently by the European Community, which resulted in two workshops on Bioelectronics, sponsored and organized by the Commission of the European Communities. The first workshop was held at the end of 1991 in Brussels, the second one at the end of November 1993, in Frankfurt (Main). The Italian leadership in the field of Bioelectronics is now acknowledged by the scientific community. This leadership role was confrrmed by the mandate given by the Commission of the European Community to Polo Nazionale Bioelettronica to carry out a feasibility study for a new Research and Development program on bioelectronics to be undertaken by the Commission in 1994-1998. The study group was composed of leading experts in the fields relevant to bioelectronics, including Nobel prize winners. The very first meeting on Bioelectronics in Italy was held in Novara on April 4-7, 1987 and was sponsored by CIREF, an Association for Industrial Strategic Research, upon the initiative of Professor C. Nicolini (at the time Science and Technology Advisor of the Italian Prime-Minister) and three top industrial Chief Executive Officers: Professor Amilcaro Collina (Montedison), Professor Umberto Rosa (SNIA-PIA T), and Dr. Pasquale Pistorio (SGS-Thompson). Highly innovative and daring was the decision by Professor Antonio Ruberti in 1988 (who at that time was the Minister for Science and Technology and is now Commissary for Research in Brussels and Vice-President of the Commission of the European Community) to start a National Program of Research on "Technologies for Bioelectronics," chaired by Professor C. Nicolini. The objectives of training and research activity of this program are constantly and soundly supported by some of the most noted experts worldwide in various fields of bioelectronics (Capasso, Faggin, Croce, Karplus, Barraud, Hopfleld, Aizawa, Wuthrich, Skryabin, Varfolomeev, Bykov) and are confrrmed by their participation in the EL.B.A. Forum. More than twenty academic and industrial centers have been involved in the extensive training of 57 young researchers working in the field of bioelectronics, initially selected in the Isle of Elba among four hundred graduates and Ph.D.s, all of whom participated in the EL.B.A. Forum Workshops. An analysis of the initial activity in the three different areas of the national program neural and submicron electronics, protein engineering, and first generation bioelectronics- vii confirmed the industrial importance of the results and prototypes obtained by the companies, research institutions and universities, the most competitive of which were present at the III CIREF Workshop at Bergamo on October 26-27, 1993. An island and an acronym (Electronics and Biotechnology Advanced) have given the name to a Scientific and Technological Park-a natural location of an expanding scientific and technological project of European dimensions. Technobiochip (a research consortium of five leading industries operational in the area of electronics and biotechnology) played the most significant role in organizing the EL.B.A. Forum Workshops on the Isle of Elba, where it's research laboratories are located (in Marciana). The level of the research activity perfonned there is undoubtedly of the highest European standards and importance in the field of bioelectronics. The numerous participants who attended the EL.B.A. Forums held in 1992-93 represented the leading industrial research organizations and academic institutions, and presented a wide and deep outline of what is now being defined as Bioelectronics, at the crossing of advanced electronics and biotechnology. viii CONTENTS From Protein Engineering to Bioelectronics ..................................................... 1 C. Nicolini On Hand-Printed Character Recognition ........................................................ 37 Zs. M. Kovacs-V., R. Guerrieri, G. Baccarani Smart Vision Chips in CCD and CCD/CMOS Technologies ................................. 49 G. Soncini, P.L. Bellutti, M. Boscardin, F. Giacomozzi, M. Gottardi, and M. Zen Ion Sensitive Field Effect Transistors: Basic Principles and Fabrication Technology ..... 55 G. Soncini, A Lavarian, A Lui, B. Margesin, V. Zanini, and M. Zen Computational Properties of Retinal Rod Photoreceptors . . . . . . . . . . . . . . . . . .. . . . . . . . .. . . . . . . . .. 63 G.M. Ratto, G. Di Schino and L. Cervetto Structure-Function Relationships in Human Growth Hormone: Theoretical and Genetic Engineering Study ......................................................................... 73 M.P. Kirpichnikov, AE. Gabrielian, A.A. Schulga, E.S. Severin and K.G. Skryabin Proteins and Enzymes from Extremophiles: Academical and Industrial Prospects ......... 79 M. Rossi Electron Transfer from Bacterial Dehydrogenases .... . . . . . . . . . .. . . . .. . . . . . . . . . . . .. . . . . . . .. . . .. 87 I.A Duine The Use of Paramagnetic Probes for NMR Investigations of Biomolecular Structures and Interactions ............................................................................ 95 M. Scarselli, G. Esposito, H. Molinari, M. Pegna, L. Zetta and N. Niccolai Use of Molecular Dynamics for the Reconstruction of Complete Structures: A Study on Thioredoxin ................................................................. 103 E.A. Carrara, A Anselmino, C. Gavotti, S. Vakula and C. Nicolini Enzyme Bioamplification ......................................................................... 111 A Rigo and M. Scarpa Electric "Contacts" between Conductors and Protein Active Sites .......................... 121 S.D. Varfolomeyev and A.I. Yaropolov From Molecular Characterization to Molecular Manufacturing and Molecular Electronics ................................................................................. 135 C. Nicolini Quaternary Chromatin-DNA Structure Imaged by Scanning Near-Field Optical Microscope: A Computer Simulation .................................................. 167 P. Facci and C. Nicolini ix