Table Of ContentFrom 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
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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
