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ADVANCED SENSOR
TECHNOLOGY
ADVANCED SENSOR
TECHNOLOGY
BIOMEDICAL,
ENVIRONMENTAL, AND
CONSTRUCTION APPLICATIONS

Edited by

AHMED BARHOUM
NanoStruc Research Group, Chemistry Department, Faculty of Science, Helwan University, Cairo,
Egypt; National Centre for Sensor Research, School of Chemical Sciences, Dublin City University,
Dublin, Ireland

ZEYNEP ALTINTAS
Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Technical University of Berlin,
Berlin, Germany; Institute of Materials Science, Faculty of Engineering, Kiel University, Kiel, Germany
Preface

Advanced Sensor Technology: Biomedical, Environmental, and


Construction Applications is appropriate for the interdisciplinary commu-
nity of researchers and practitioners interested in developing sensor
technologies. The book is a valuable reference for materials scientists,
biologists, and medical, chemical, biomedical, manufacturing, and
mechanical engineers working in the research and development indus-
try, as well as academics interested in learning more about future global
markets, emerging applications, and the technology of sensor-based sys-
tems. The authors address the economics of sensor technology, includ-
ing the fabrication of chemical sensors, biosensors, and nanosensors.
Topics are covered comprehensively and presented in a logical manner
for the benefit of the reader.

xxi
List of contributors

Abdelwaheb Chatti Laboratory of Biochemistry and Molecular Biology,


Faculty of Sciences of Bizerte, University of Carthage, Jarzouna, Tunisia
Abdul Shaban Research Centre for Natural Sciences, Institute of Materials and
Environmental Chemistry, Budapest, Hungary
Afef Gamraoui Laboratory of Biochemistry and Molecular Biology, Faculty of
Sciences of Bizerte, University of Carthage, Jarzouna, Tunisia
Ahmed Barhoum NanoStruc Research Group, Chemistry Department, Faculty
of Science, Helwan University, Cairo, Egypt; National Centre for Sensor
Research, School of Chemical Sciences, Dublin City University, Dublin,
Ireland
Aida Mousavi Research Laboratory of Spectrometry & Micro and Nano
Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Amina Othmani Faculty of Sciences of Monastir, University of Monastir,
Monastir, Tunisia
Aysu Tolun Institute of Chemistry, Faculty of Natural Sciences and
Mathematics, Technical University of Berlin, Berlin, Germany
Azam Bagheri Pebdeni Department of Life Science Engineering, Faculty of
New Sciences & Technologies, University of Tehran, Tehran, Iran
Aziz Amine Laboratory of Process Engineering and Environment, Faculty of
Sciences and Techniques, Hassan II University of Casablanca, Mohammedia,
Morocco
Bahar Saboorizadeh Research Laboratory of Spectrometry & Micro and Nano
Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Bora Garipcan Institute of Biomedical Engineering, Boğaziçi University,
İstanbul, Turkey
Cansu İlke Kuru Ege University, Faculty of Science, Department of
Biochemistry, Izmir, Turkey
Ecenaz Bilgen Department of Chemistry, Middle East Technical University,
Çankaya, Ankara, Turkey
Ekin Sehit Institute of Chemistry, Faculty of Natural Sciences and
Mathematics, Technical University of Berlin, Berlin, Germany; Institute of
Materials Science, Faculty of Engineering, Kiel University, Kiel, Germany
Fahimeh Nojoki Department of Life Science Engineering, Faculty of New
Sciences & Technologies, University of Tehran, Tehran, Iran

xiii
xiv List of contributors

Fereshteh Amourizi Research Laboratory of Spectrometry & Micro and Nano


Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Francisco J. Barba Nutrition and Food Science Area, Preventive Medicine and
Public Health, Food Sciences, Toxicology and Forensic Medicine Department,
Faculty of Pharmacy, Universitat de València, València, Spain
Fulden Ulucan-Karnak Ege University, Faculty of Science, Department of
Biochemistry, Izmir, Turkey
Gilbert Tang School of Aerospace, Transport and Manufacturing, Cranfield
University, Cranfield, United Kingdom
Hayriye Öztatlı Institute of Biomedical Engineering, Boğaziçi University,
İstanbul, Turkey
Ivan Petrunin School of Aerospace, Transport and Manufacturing, Cranfield
University, Cranfield, United Kingdom
Javad Shabani Shayeh Protein Research Center, Shahid Beheshti University,
Tehran, Iran
Judit Telegdi Research Centre for Natural Sciences, Institute of Materials and
Environmental Chemistry, Budapest, Hungary; Óbuda University, Faculty of
Light Industry and Environmental Engineering, Budapest, Hungary
Kaiyu He State Key Laboratory for Managing Biotic and Chemical Threats to
the Quality and Safety of Agro-products; Institute of Agro-product Safety and
Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, P.R. China
Kakali Ghoshal Department of Medicine, Division of Nephrology and
Hypertension, Vanderbilt University School of Medicine, Nashville, TN,
United States
Kheibar Dashtian Research Laboratory of Spectrometry & Micro and Nano
Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Larbi Eddaif Óbuda University, Faculty of Light Industry and Environmental
Engineering, Budapest, Hungary; Research Centre for Natural Sciences,
Institute of Materials and Environmental Chemistry, Budapest, Hungary
Liu Wang State Key Laboratory for Managing Biotic and Chemical Threats to
the Quality and Safety of Agro-products; Institute of Agro-product Safety and
Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, P.R. China
Maria Helena de Sá CIQUP-Chemistry Research Centre of the University of
Porto, Department of Chemistry and Biochemistry, Faculty of Sciences,
University of Porto, Porto, Portugal
Maryam Amoo Nanotechnology Group, Department of Material Engineering,
Isfahan University of Technology, Isfahan, Iran
Mehran Habibi Rezaei Department of Cell & Molecular Biology, School of
Biology, College of Science, University of Tehran, Tehran, Iran
Mehrdad Forough Department of Chemistry, Middle East Technical
University, Çankaya, Ankara, Turkey
List of contributors xv

Mehrnoush Dianatkhah Department of Clinical Pharmacy, Faculty of


Pharmacy, Isfahan University of Medical Science, Isfahan, Iran
Muqsit Pirzada Institute of Materials Science, Faculty of Engineering, Kiel
University, Kiel, Germany; Institute of Chemistry, Faculty of Natural Sciences
and Mathematics, Technical University of Berlin, Berlin, Germany
Narjiss Seddaoui Laboratory of Process Engineering and Environment,
Faculty of Sciences and Techniques, Hassan II University of Casablanca,
Mohammedia, Morocco
Navvabeh Salarizadeh Department of Cell & Molecular Biology, School of
Biology, College of Science, University of Tehran, Tehran, Iran; Department of
Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical
Sciences, Tehran, Iran
Neda Shahbazi Research Laboratory of Spectrometry & Micro and Nano
Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Nissem Abdeljelil Laboratory of Biochemistry and Molecular Biology, Faculty
of Sciences of Bizerte, University of Carthage, Jarzouna, Tunisia
Omer Sadak Department of Electrical and Electronics Engineering, Ardahan
University, Ardahan, Turkey
Özgül Persil Çetinkol Department of Chemistry, Middle East Technical
University, Çankaya, Ankara, Turkey
Qingxin Hui Cranfield Water Science Institute, School of Water, Energy and
Environment, Cranfield University, Bedford, United Kingdom
Richard Luxton Institute of Bio-Sensing Technology, University of the West of
England, Bristol, United Kingdom
Rouholah Zare-Dorabei Research Laboratory of Spectrometry & Micro and
Nano Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Sajjad Shojai Department of Animal Science, School of Biology, College of
Science, University of Tehran, Tehran, Iran
Sana Safari Astaraei Research Laboratory of Spectrometry & Micro and Nano
Extraction, Department of Chemistry, Iran University of Science and
Technology, Tehran, Iran
Selma Hamimed Laboratory of Biochemistry and Molecular Biology, Faculty
of Sciences of Bizerte, University of Carthage, Jarzouna, Tunisia
Seyed Jalal Zargar Department of Cell & Molecular Biology, School of
Biology, College of Science, University of Tehran, Tehran, Iran
Seyed Mohammad Taghi Gharibzahedi IInstitute of Chemistry, Faculty of
Natural Sciences and Mathematics, Technical University of Berlin, Berlin,
Germany; Institute of Materials Science, Faculty of Engineering, Kiel
University, Kiel, Germany
Sinan Akgöl Ege University, Faculty of Science, Department of Biochemistry,
Izmir, Turkey
xvi List of contributors

Vahid Mofid Department of Food Sciences & Technology, National Nutrition


and Food Technology Research Institute, Faculty of Nutrition Sciences and
Food Technology, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
Wenliang Li Cranfield Water Science Institute, School of Water, Energy and
Environment, Cranfield University, Bedford, United Kingdom
Xiahong Xu State Key Laboratory for Managing Biotic and Chemical Threats
to the Quality and Safety of Agro-products; Institute of Agro-product Safety
and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, P.R.
China
Yethreb Mahjoubi Laboratory of Plant Toxicology and Environmental
Microbiology, Faculty of Sciences of Bizerte, University of Carthage,
Zarzouna, Tunisia
Yuwei Pan Cranfield Water Science Institute, School of Water, Energy and
Environment, Cranfield University, Bedford, United Kingdom
Zahra Goli-Malekabadi Bioengineering Center for Cancer, Department of
Mechanical Engineering, Isfahan University of Technology, Isfahan, Iran;
Department of Biomedical Engineering, Amirkabir University of Technology,
Tehran, Iran
Zeynep Altintas Institute of Materials Science, Faculty of Engineering, Kiel
University, Kiel, Germany; Institute of Chemistry, Faculty of Natural Sciences
and Mathematics, Technical University of Berlin, Berlin, Germany
Zhugen Yang Cranfield Water Science Institute, School of Water, Energy and
Environment, Cranfield University, Bedford, United Kingdom
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Contents

List of contributors xiii


About the editors xvii
Preface xxi

1
Fundamental aspects
1. Sensor technology: past, present, and future 3
MUQSIT PIRZADA AND ZEYNEP ALTINTAS

1.1 Introduction 3
1.2 Milestones in sensor development 5
1.3 State-of-the-art in sensor technology 7
1.4 The way ahead in sensing opportunities 9
1.5 Conclusions and remarks 11
Acknowledgments 12
References 12

2. Fundamentals of sensor technology 17


LARBI EDDAIF AND ABDUL SHABAN

2.1 Sensor, actuator, and transducer fundamentals 17


2.2 Sensors’ classification 23
2.3 Sensor applications 31
2.4 Innovative sensor technologies 39
2.5 Conclusion and future aspects 41
References 42

2
Biomedical applications
3. Biosensors for virus detection 53
EKIN SEHIT AND ZEYNEP ALTINTAS

3.1 Introduction 53
3.2 Antibody-based biosensors for virus detection 57
3.3 Nucleic acid-based biosensors for virus detection 60

v
vi Contents

3.4 Peptide-based biosensors for virus detection 65


3.5 Molecularly imprinted polymer-based biosensors for virus detection 69
3.6 Conclusion and remarks 73
Acknowledgments 74
References 74

4. Biosensors for bacteria detection 81


YUWEI PAN, WENLIANG LI, QINGXIN HUI AND ZHUGEN YANG

4.1 Introduction 81
4.2 Whole-cell biosensors for bacteria detection 82
4.3 Nanomaterials-based biosensors for bacteria detection 85
4.4 Various biosensors for bacteria detection 90
4.5 Integrated biosensing platforms for multiplexed bacteria detection 112
4.6 Conclusion and perspectives 115
References 116

5. Biosensors for drug of abuse detection 125


KHEIBAR DASHTIAN, FERESHTEH AMOURIZI, NEDA SHAHBAZI, AIDA MOUSAVI,
BAHAR SABOORIZADEH, SANA SAFARI ASTARAEI AND ROUHOLAH ZARE-DORABEI

5.1 Introduction 125


5.2 Drug biosensing 126
5.3 Conclusion and remarks 160
References 161
Further reading 172

6. Biosensors for nucleic acid detection 173


MEHRDAD FOROUGH, ECENAZ BILGEN AND ÖZGÜL PERSIL ÇETINKOL

6.1 Introduction 173


6.2 Optical nucleic acid biosensors: principles and feasibilities 175
6.3 Electrochemical nucleic acid biosensors 188
6.4 Strategies for improving the sensitivity of nucleic acid biosensors 193
6.5 CRISPR/Cas-assisted biosensing platforms for nucleic acid detection 202
6.6 Biosensor applications based on the nucleic acid structure 205
6.7 Conclusion and outlook 212
References 213

7. Biosensors for glucose detection 235


EKIN SEHIT AND ZEYNEP ALTINTAS

7.1 Introduction 235


7.2 Electrochemical glucose biosensors 237
7.3 Optical glucose biosensors 244
7.4 Other glucose biosensors 251
7.5 Conclusion and remarks 254
Acknowledgments 254
References 254
Contents vii

8. Recent advances in biosensing technologies for detecting


hormones 261
KAKALI GHOSHAL

8.1 Introduction 261


8.2 Biosensor types based on biorecognition elements 263
8.3 Biosensors based on transducers in hormone detection 264
8.4 Discussion and conclusion 286
Acknowledgment 290
Conflicts of interest 290
References 290

9. Biosensors for cancer biomarker detection 297


MUQSIT PIRZADA AND ZEYNEP ALTINTAS

9.1 Introduction 297


9.2 Cancer progress and biomarkers 300
9.3 Electrochemical biosensors for cancer biomarker detection 306
9.4 Optical biosensors for cancer biomarker detection 311
9.5 Piezoelectric biosensors for cancer biomarker detection 316
9.6 Other biosensors for cancer biomarker detection 319
9.7 Conclusion and remarks 320
Acknowledgments 322
References 322

10. Classical and new candidate biomarkers for developing


biosensors in diagnosing diabetes and prediabetes; past, present
and future 337
NAVVABEH SALARIZADEH, SAJJAD SHOJAI, AZAM BAGHERI PEBDENI, FAHIMEH NOJOKI,
SEYED JALAL ZARGAR AND MEHRAN HABIBI REZAEI

10.1 Introduction to diabetes mellitus 337


10.2 Pathophysiology of diabetes 339
10.3 Glucose as a diabetes biomarker (history, accuracy, advantages, and
disadvantages) 345
10.4 Glycated hemoglobin and glycated albumin as diabetes biomarkers 355
10.5 Novel biomarkers/metabolites in diabetes and associated complications 363
10.6 Conclusion 372
References 373

11. Biosensors for drug detection 383


ZAHRA GOLI-MALEKABADI, NAVVABEH SALARIZADEH, MEHRNOUSH DIANATKHAH,
MARYAM AMOO AND JAVAD SHABANI SHAYEH

11.1 Introduction 383


11.2 Criteria of an ideal method for drug analysis 387
viii Contents

11.3 Biosensor design 389


11.4 Biosensors for drug detection 392
11.5 Recent trends in biosensors for drug detection 406
11.6 Conclusion 407
References 408

12. Micro alcohol fuel cells towards autonomous electrochemical


sensors 413
MARIA HELENA DE SÁ

12.1 Introduction 413


12.2 Fundamentals 418
12.3 Design and flow considerations 423
12.4 Fuels electrooxidation and micropower generation 435
12.5 Examples toward sensing applications 452
12.6 Conclusion and future outlook 458
References 458

13. Biosensors for organs-on-a-chip and organoids 471


HAYRIYE ÖZTATLI, ZEYNEP ALTINTAS AND BORA GARIPCAN

13.1 Introduction 471


13.2 The use of biosensors in organotypic models 473
13.3 Biosensing technologies for monitoring organotypic models 476
13.4 Applications of biosensors in in vitro culture platforms of organotypic
models 488
13.5 Conclusion and future perspectives 500
Acknowledgments 501
References 501

3
Environmental applications
14. Sensors for water and wastewater monitoring 517
ABDUL SHABAN, LARBI EDDAIF AND JUDIT TELEGDI

14.1 Wastewater pollutants 517


14.2 Sources of water pollutants 517
14.3 Types of water pollutants 518
14.4 Indicators of water pollution 522
14.5 Analytical methods for the detection of wastewater pollutants 528
14.6 Chemical sensors in water pollutant detection 537
14.7 Electrochemical sensors in water pollutant detection 541
14.8 Optical biosensors for water pollution detection 546
14.9 Conclusion 555
References 556
Contents ix

15. Chemical sensing of heavy metals in water 565


OMER SADAK

15.1 Introduction 565


15.2 Heavy metal toxicity ranges and mechanism in living cells 567
15.3 Heavy metal measurement methods in water and their performance 569
15.4 Current trends in heavy metal monitoring 582
15.5 Current limitations and future prospective 584
15.6 Conclusion 585
References 585

16. Chemical sensing of food phenolics and antioxidant capacity 593


AYSU TOLUN AND ZEYNEP ALTINTAS

16.1 Introduction 593


16.2 Conventional methods for the determination of total phenolics and
antioxidant capacity 596
16.3 Novel sensing methods of total phenolics and antioxidant capacity 597
16.4 Conclusion 635
Acknowledgments 636
References 636

17. Chemical sensing of pesticides in water 647


KAIYU HE, LIU WANG AND XIAHONG XU

17.1 Introduction 647


17.2 Colorimetric sensors for detection of pesticides 649
17.3 Fluorescent sensors for detection of pesticides 652
17.4 Raman sensors for detection of pesticides 654
17.5 Electrochemical sensors for detection of pesticides 657
17.6 Chemiluminescent sensors for detection of pesticides 660
17.7 Electrochemiluminescent sensors for detection of pesticides 662
17.8 Piezoelectric sensors for detection of pesticides 663
17.9 Conclusion and future perspectives 665
References 666

18. Chemical sensors and biosensors for soil analysis: principles,


challenges, and emerging applications 669
SELMA HAMIMED, YETHREB MAHJOUBI, NISSEM ABDELJELIL, AFEF GAMRAOUI,
AMINA OTHMANI, AHMED BARHOUM AND ABDELWAHEB CHATTI

18.1 Introduction 669


18.2 Detection of soil nutrients 671
18.3 Detection of pH 673
18.4 Detection of soil moisture 675
18.5 Detection of organic matter 676
18.6 Detection of inorganic pollutants 680
x Contents

18.7 Soil-borne disease using a microbial biosensor 681


18.8 Challenges and future perspectives 692
18.9 Conclusion 693
References 693

19. Recent advances in sensor and biosensor technologies for


adulteration detection 699
NARJISS SEDDAOUI AND AZIZ AMINE

19.1 Introduction 699


19.2 Adulteration: a global scam and health threat 700
19.3 Conventional analytical techniques for adulterants detection 707
19.4 Recent trends in adulteration detection 708
19.5 Conclusions and remarks 725
References 726

4
Construction and other applications
20. Biosensing technology in food production and processing 743
SEYED MOHAMMAD TAGHI GHARIBZAHEDI, FRANCISCO J. BARBA, VAHID MOFID AND
ZEYNEP ALTINTAS

20.1 Introduction 743


20.2 Biosensors and food quality 758
20.3 Biosensors and food safety 786
20.4 Future prospectives 798
20.5 Conclusion 799
Acknowledgments 799
References 800

21. Sensors for aerial, automotive, and robotic applications 825


IVAN PETRUNIN AND GILBERT TANG

21.1 Introduction 825


21.2 Optical sensors 826
21.3 Inertial sensors 831
21.4 Radio frequency sensors 833
21.5 Magnetic and acoustic sensors 839
21.6 Timing sources 842
21.7 Final remarks 845
References 846

22. Challenges and future aspects of sensor technology 853


RICHARD LUXTON

22.1 Introduction 853


Contents xi

22.2 Technology drivers 855


22.3 Commercialization 865
22.4 In conclusion 869
References 870
Further reading 874

23. Sensor commercialization and global market 879


FULDEN ULUCAN-KARNAK, CANSU İLKE KURU AND SINAN AKGÖL

23.1 Introduction 879


23.2 Trends in sensing technologies 881
23.3 Sensing research and development 889
23.4 Commercialization pathway 890
23.5 Sensors in various industrial areas and global market shares 899
23.6 Conclusion 906
References 907

Index 917
About the editors

Prof. Dr. Ahmed Barhoum: NanoStruc Research


Group, Chemistry Department, Faculty of
Science, Helwan University, Cairo, Egypt;
National Centre for Sensor Research, School of
Chemical Sciences, Dublin City University,
Dublin, Ireland
Ahmed Barhoum is the head of the Nanostruc
Research Group, Chemistry Department at the
Helwan University (Egypt). He leads an interdis-
ciplinary research group in the synthesis of nano-
particles, imprinted polymers, nanofibers, and
thin films for catalysis, drug delivery, and electrochemical biosensing.
He obtained his PhD and postdoc fellow in chemical sciences from the
Department of Materials and Chemistry (MACH), Vrije Universiteit
Brussel (Belgium). He is currently working at the School of Chemical
Sciences (SCS), and a member of the National Centre for Sensor
Research (NCSR), Fraunhofer Project Centre (FPC), and Nano Research
Facility (NRF) at Dublin City University (Ireland). He has received sev-
eral scientific awards and prizes for his academic excellence: Helwan
University Prizes (2020 and 2019), Irish Research Council (2020),
Chinese Academy of Science Fellowship (China, 2019), Institut français
d’Égypte Fellowships (France, 2018 and 2020), Research Foundation
Flanders Fellowships (Belgium, 2015 and 2016), Medastar Erasmus
Mundus (Belgium, 2012), Welcome Erasmus Mundus (Italy, 2012), Gold
Medal from the Egyptian Syndicate of Scientific Professions (2007),
Gold Medal from the Helwan University (2007), and many more. He
also serves as an expert evaluator for the National Science Centre
(Poland), Czech Science Foundation (Russia), Swiss National Science
Foundation (SNSF, Switzerland), and Innovators Support Fund (ISF,
Egypt) and examiner for international student’s work (Egypt, India,
Australia, etc.). He is on the editorial board of Frontiers in Bioengineering
and Biotechnology, Frontiers in Nanotechnology, Nanomaterials, and
Frontiers in Materials and editor of 12 handbooks published by Elsevier
and Springer Nature. He has secured 18 research grants (PI/Co-PI of 10
funded projects and member of 8 projects) from Egypt (ASRT & STDF),
China (CAS), Japan (JSPS), the United States (NSF & US-Aid), Belgium
(SIM & FWO), Germany (AGYA), and France (Imhotep), among others.

xvii
xviii About the editors

He has coauthored 150 papers and published in top-tier journals,


including Journal of Materials Chemistry A, ACS Applied Materials &
Interfaces, Applied Materials Today, Nanoscale, Carbohydrate Polymers,
Materials Science and Engineering: C, Journal of Colloid and Interface
Science, out of which many have been highlighted in research highlights,
news, and journal cover articles. His handbook Emerging Applications of
Nanoparticles, Elsevier, has been featured on CNN Forbes, and Inc, and
is among the top best nanostructures books of all time.

Prof. Dr. Zeynep Altintas: Institute of Chemistry,


Faculty of Natural Sciences and Mathematics,
Technical University of Berlin, Berlin, Germany;
Institute of Materials Science, Faculty of
Engineering, Kiel University, Kiel, Germany
Prof. Zeynep Altintas is the chair of
Bioinspired Materials and Biosensor Technologies
at the University of Kiel. She has been the head of
Biosensors Group at the Technical University of
Berlin since 2016. She completed her PhD at the
age of 25 with the outstanding PhD student
award. Her PhD period brought her several other research prizes and
fellowships. Following a 1-year postdoc position at the Cranfield
Biotechnology Centre, she continued her academic career as a faculty
member of biomedical engineering at the Cranfield University (the
United Kingdom) until 2016. She leads an interdisciplinary research
group in the domains of biosensor technologies, computational chemis-
try, receptor design, functional polymers and their applications in (bio)
chemical sciences, nanomaterials applications, and design, synthesis,
and characterization of biomimetic materials. She has .170 publications
in these fields, including books, journal articles, book chapters, patent
applications, and conference papers. She has supervised more than 35
PhD and MSc students and mentored 7 postdoctoral fellows. She has
delivered plenary and invited talks at numerous international confer-
ences and world-renowned institutes to date. Her reputation is recog-
nized by many prestigious international awards and grants for her
research. Among others are the Life Science Bridge Award (along with
h100,000 prize money), the Royal Society of Chemistry Research Award,
the Marie Curie Individual Fellowship for Experienced Researchers, the
TUBITAK Fellowship for Internationally Recognised Scientists, the
Travel Grants from the British Council (2014a16), and several best pos-
ters, oral presentation, and paper awards. She serves as a referee for
numerous high-impact journals and for several funding research institu-
tions including the European Union (EU), the German Research
About the editors xix

Foundation (DFG), the Dutch Research Council (NWO), the Israel


Science Foundation (ISF), the French National Research Agency (ANR),
the German Federal Ministry of Education and Research (BMBF) & EU
Cofund Projects, and the Wisconsin Groundwater Coordinating Council
(United States). She is an editorial board member of Biosensors and
Bioelectronics, Sensing and Bio-Sensing Research, Scientific Reports,
Micromachines, and Materials. She takes part in the organization and sci-
entific committees of several international conferences. She is also a
member of RSC since 2012 and holds visiting professorships in various
EU countries.
C H A P T E R

1
Sensor technology: past, present,
and future
Muqsit Pirzada1,2 and Zeynep Altintas1,2
1
Institute of Chemistry, Faculty of Natural Sciences and Mathematics,
Technical University of Berlin, Berlin, Germany, 2Institute of Materials
Science, Faculty of Engineering, Kiel University, Kiel, Germany

1.1 Introduction

Modern sensors are vastly different from the primitive oxygen elec-
trode developed by Clark nearly seven decades ago [1]. A survey of all
databases from Web of Science (keywords: sensor/s OR biosensor/s)
reveals that interest in sensor technology has exploded in recent times
with nearly 1.5 million papers published within the last 40 years. Of these,
more than a million have just been published since 2009. This exponential
progress (Fig. 1.1) can be attributed to the multifold improvement in sev-
eral scientific disciplines such as electrochemistry, optics, nanotechnology,
molecular dynamics, and proteomics. Another trigger for this success is
the rising demand for analyte recognition across various fields of applica-
tion. For example, identifying and analyzing contaminants in food pro-
duction is a prerequisite to ensuring a long shelf-life as well as consumer
safety. Accumulation of microbial metabolic byproducts helps identify the
freshness of meat and fish [2]. The levels of such metabolites and proteins
in living beings may also act as early indicators of different health condi-
tions [3]. Quantifying these markers helps identify diseases, risk factors,
pregnancy as well as drug efficacy. Biosensors also help monitor the effec-
tiveness of clinical therapies thereby enabling healthcare professionals to
customize patient-specific treatments. The trend is also reflected in the
commercial progress of sensing instruments where the contribution of bio-
sensors has swelled from US$ 5 million to US$ 13 billion within three

Advanced Sensor Technology


DOI: https://doi.org/10.1016/B978-0-323-90222-9.00006-6 3 © 2023 Elsevier Inc. All rights reserved.
4 1. Sensor technology: past, present, and future

140000 800

120000
600 Sensors
Point of care

Publications
100000
400
Publications

80000
200
60000

0
40000 1990 1995 2000 2005 2010 2015 2020
Year
20000

0
1975 1980 1985 1990 1995 2000 2005 2010 2015 2020
Year

FIGURE 1.1 Research works on sensors published between 1975 and 2020. Inset:
Research works on sensors for point-of-care testing purposes from 1990 to 2020. Source:
Data from Web of Science.

decades [4]. Since the development of the first commercial biosensor in


1975, the number and variety of sensors have consistently increased to
more than 40,000 products for in vitro diagnostics alone [5].
Although conventional diagnostics are still performed at centralized
facilities by experienced professionals, the crippling deficiency of material
and financial resources in underdeveloped and developing nations makes
timely disease recognition not only time-consuming but also expensive and
inaccessible to the general public. Therefore the World Health Organization
has encouraged the development of point-of-care-tests (POCT) that meet
the ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and
robust, Equipment-free and Deliverable to end-users) criteria and can be
performed by the consumer in a nonclinical setting. As a result, the
research and development of POCT devices have multiplied 130-fold from
1990 to 2020 (Fig. 1.1, inset). Sensor technology is therefore gravitating
toward paper-based assays, lateral flow-tests, smartphone-based detection,
and many similar approaches that rely on ubiquitous raw materials and
instruments. Today, arduous experimental optimizations are being replaced
with computational simulations. Several different types of nanomaterials
are being incorporated in biosensors to amplify their signal, reduce the
response time and improve the binding affinity [6]. Miniaturization of bio-
sensors using microfluidic technology helps in reducing the sample volume
required for analysis. Microfluidic technology is an integral part of lab-on-
a-chip and organ-on-a-chip systems.
The specificity of sensing systems to recognize a typical analyte can
be exploited for targeted drug delivery and therapy. Such approaches
reduce the adverse side-effects that are quotidian in the treatment of

1. Fundamental aspects
1.2 Milestones in sensor development 5

cancer patients. In vivo sensing is also useful in the development of arti-


ficial organs to regulate organ behavior in response to various intracel-
lular signaling events [7]. The ongoing global coronavirus pandemic has
also directed renewed interest toward biosensors as potential tools for
identifying and curbing water as well as air pollution [8,9].

1.2 Milestones in sensor development

The current ubiquity of sensors should not be considered as a stand-


alone success resulting solely from Cramer’s work on the glass electrode
[10] or even Clark’s seminal research on biosensors [1,11]. While these
works laid the groundwork on which sensor technology is built, the lat-
est developments in biosensors are the products of advancements, dis-
coveries, and inventions across a gamut of scientific areas. A few of
these concepts even predate Clark’s work but have still emerged useful
in sensor development. For example, while Polyakov’s group was work-
ing with silica particles in 1931, they observed that particles from which
the additives were removed showed enhanced adsorption for the addi-
tives in comparison to structurally analogous ligands [12]. Dickey
substituted these additives with dyes as templates [13]. This concept of
additive memory evolved into molecular imprinting technology, a pop-
ular technique for cost-effective molecular recognition. Molecular
imprinting has itself undergone several improvements in the nine dec-
ades since its inception. The silica particles have largely been replaced
with organic polymers since 1972 [14]. Therefore Mosbach’s group pro-
posed using such molecularly imprinted polymers (MIPs) to mimic anti-
bodies [15].
Molecular imprinting is not a singular field. The impetus to make
sensors “more intelligent” was the driving force behind the diversifica-
tion of sensor technology. In its early phase, sensor development was
an eccentric notion involving the integration of biomolecules such as
enzymes to electrochemical sensing elements such as electrodes.
Although the first batch of sensors relied on either voltammetry or
amperometry, other electrochemical methods such as potentiometry
were soon explored. The primitive enzyme electrodes of the 1960s were
improvised by Professor Rechnitz in 1971 by placing them in an
inverted configuration for betaglucosidase-mediated amygdaline sens-
ing [16]. This ion-selective electrode sparked a renaissance age in sensor
development where multiple combinations of the transducer and the
biological element were probed.
The variations in these elements and their combinations are still
ongoing. Sensors have been developed with piezoelectric, thermal, and
then optical transducers. This continuous evolution facilitated the

1. Fundamental aspects
6 1. Sensor technology: past, present, and future

development of the first in vivo ultrasound biosensor in 2020 [17]. The


selection of receptors has also evolved from enzymes to antibodies,
nucleic acids, whole cells, aptamers, affibodies, phages, and synthetic
ligands. Although the enzymes were the receptor of choice in the first
few years of sensor development and were used by several eminent
researchers like Clark [11], Updike and Hicks [18], Guilbault and
Montalvo [19], antibody-assisted biomolecule recognition was also being
investigated in parallel. The antibody-antigen interaction had remained
an enigma since the discovery of antibodies in 1890 [20]. Once these
interactions were theorized by Goldberg in 1952 [21], their suitability for
disease recognition was soon investigated. Within four years, the latex
agglutination assay was developed that relied on these interactions to
diagnose rheumatoid arthritis. Yalow and Berson subsequently devel-
oped the first immunoassay, a radioimmunoassay, in 1959 for which
Yalow was awarded the Nobel Prize in 1977 [22]. Since the radioimmu-
noassay was not patented, assays for several different analytes were
soon developed. As this technique involved antibody labeling with
radioactive isotopes, alternative labels were studied in the 1960s and
antibody-enzyme links were reported in 1966 [23,24], which laid the
groundwork for the first enzyme-linked immunosorbent assay within
the next 5 years [25]. Another pivotal milestone in immunosensing was
the development of monoclonal antibodies by Köhler and Milstein in
1975 [26]. The process was revolutionary and mitigated the pertinent
issues of limited antibody supply and unavailability culminating in a
Nobel Prize in medicine for both the researchers in 1984. Some of the
popular assays developed during this time are illustrated in Fig. 1.2.
Similar milestones were also achieved in the field of detection using
nucleic acids as well as whole cells or microbes. Enzymes, antibodies,
nucleic acids, and whole cells are generally considered conventional

FIGURE 1.2 (A) Different types of enzyme-linked immunosorbent assays (ELISA); (B)
Gel electrophoresis, which is the basis of Southern, Western, Northern, and Eastern blot
tests; (C) Antigen recognition by radioimmunoassay.

1. Fundamental aspects
1.3 State-of-the-art in sensor technology 7

receptors. While enzymatic receptors function due to catalysis, all other


elements perform affinity-based recognition. Recent receptors such as
synthetic antibodies, phages, affibodies, and aptamers are emerging as
promising substitutes to the conventional receptors and may entirely
replace them in the future.

1.3 State-of-the-art in sensor technology

The prevalence and successful application of sensors are incumbent


on several factors such as their cost, response time, sensitivity, specific-
ity in the sensing medium, and their ability to detect multiple analytes.
The drive to attain ultrasensitivity has resulted in the integration of
several unconventional technologies into sensor development. For
example, the incorporation of nanomaterials to sensing platforms has
enabled the fabrication of sensors with high sensitivity and specificity.
Nanomaterials are materials with at least one of their dimensions
between 1 and 100 nm [6]. Owing to their small size, nanomaterials
exhibit an exceptionally high surface area-to-volume ratio. Smaller
nanomaterials such as nanoclusters and quantum dots have more atoms
on their surface in comparison to the bulk. The high-energy electrons
from these surfaces give rise to interesting plasmonic and electronic
properties. Nanomaterials can act as synthetic atoms and their proper-
ties can be tuned by controlling their size, shape, or interparticle dis-
tance. For example, the distance between a quantum dot and a gold
nanoparticle can be modulated with linkers to determine the optimal
distance for maximum localized surface plasmon resonance [27]. The
incorporation of nanoparticles into the sensing platform also helps
amplify the signal response significantly [3]. Nanomaterials hold the
key to sensor miniaturization since they can be exploited as receptors,
transducers, labels, fluorophores, and signal amplification tags [28–31].
Nanotechnology has therefore achieved popularity not only among sen-
sor developers but also among the scientific community as a whole.
This recognition is evident with the multitude of Nobel Prizes awarded
for research in this area such as Kroto, Curl, and Smalley’s discovery of
buckminsterfullerene (Chemistry, 1996), Fert and Gruenberg’s discovery
of giant magnetoresistance (Physics, 2007), Geim and Noselov’s experi-
ments on graphene (Physics, 2010), and Sauvage, Stoddart, and
Feringa’s synthesis and research on molecular machines (Chemistry,
2016). A brief survey of the Scopus database (keywords: sensor/s OR
biosensor/s AND nanomaterial/s) across all fields reveals that just
within the two decades since 2001, 167,774 documents were published
on nanomaterial-mediated sensors and 129,300 are research articles.
While only 85 of these documents belong to 2001, the number rose

1. Fundamental aspects
8 1. Sensor technology: past, present, and future

35000

30000
Publications
25000
Publications

20000

15000

10000

5000

0
2000 2005 2010 2015 2020
Year

FIGURE 1.3 Research works using nanomaterials in sensor technology from 2000 to
2020. Source: Data from Scopus.

rapidly with 4183 and 31,174 documents reported annually in 2010 and
2020, respectively (Fig. 1.3).
Mathematical modeling is another emerging tool that is useful for
fabricating biosensing platforms with desired features. It allows the
optimization of multiple criteria within the biochemical system such as
enhancing the productivity of enzymes by determining the accurate
temperature and pH required for catalytic recognition. Computational
selection of nucleic acid probes by quantifying the interactions between
Watson-Crick base pairs facilitates the generation of target-specific and
ultrasensitive genosensors [32]. Cascade networks can thus be generated
to perform divergent reactions by exploiting the compatibility between
various biomolecules. In silico biocomputation has also been adopted
for systems that involve proteins [33], aptamers [34], whole cells [35] as
well as MIPs [36]. Molecular simulations often compute the attractive
and repulsive forces of biomolecular electron clouds to predict the state
of material during the sensing event. For example, the group of Altintas
simulated different surface epitopes of a protein to select the most sta-
bile peptide sequence as templates for molecular imprints [36]. Such
simulations aid in elucidating solvent effects [37] as well as the nature
of receptor-ligand interactions [38]. Biocomputation in association with
logic-mediated operations encourages the development of artificial neu-
ral networks. These intelligent systems, when integrated into smart
stimuli-responsive materials, are capable of sensing and subsequently
actuating [32]. In silico designing of biosensors considerably reduces the
experimental load, material consumption as well as optimization and
development time.

1. Fundamental aspects
1.4 The way ahead in sensing opportunities 9

The binding affinity and specificity are two essential features of the
receptor that enable molecule recognition at low concentrations in the
presence of competent interfering molecules. Aptamers are oligonucleo-
tides or peptides that specifically bind to a target nucleotide, protein, or
cell. They belong to the class of novel receptors along with phages,
MIPs, and affibodies. Although the technology for aptamer synthesis
and enrichment (systematic evolution of ligands by exponential enrich-
ment or “SELEX”) was already developed in 1990, they were first
employed for biosensing only in 1998 [39,40]. However, aptamers have
become commonplace as receptors since then and have already sur-
passed nucleotides such as deoxyribonucleic acid (DNA) and ribonu-
cleic acid (RNA). The ongoing trend on Scopus (keywords: biosensor
“AND” ,receptor type.) reflects the potential for aptamers to surpass
antibodies as the receptor of choice within the next few decades.
Similarly, bacteriophages are also suitable candidates due to their high
affinity for bacterial proteins. The phage display technique was first
reported by Gregory Smith in 1985 [41] and further developed by
Gregory Winter for which both of them shared the Nobel Prize in chem-
istry in 2018. The phage display technique involves the insertion of a
gene, which encodes a protein or antibody of interest, in bacteriophage
capsid protein. Analogous to SELEX, phage display is a promising
in vitro technique for protein selection.

1.4 The way ahead in sensing opportunities

The ongoing pandemic and the pressure on the healthcare system


resulting from it have accelerated the research on POCT. Microfluidic
systems can be easily patterned on inexpensive substrates such as
papers or membranes to generate lateral flow assays. The simplicity,
mobility, and affordability of lateral flow assays make them ideal for
disease detection in resource-limited settings. For example, the necessity
of a coronavirus disease (COVID-19) test report has become a prerequi-
site for travel, work as well as schools and the usual polymerase chain
reaction assay is expensive, time-consuming, and complicated. Rapid
lateral flow immunoassays for detecting the coronavirus antigen can be
mass-produced and are very simple to operate by the end-consumer
[42]. They are therefore transforming into excellent COVID-19 screening
tests. It is expected that just like the case of home pregnancy kits, dis-
ease testing on lateral flow strips may also become quotidian especially
in developing nations (Fig. 1.4).
Another promising strategy is the use of MIPs as synthetic
antibodies for protein recognition. Though Mosbach proposed the idea
for drug recognition back in the 1990s, protein recognition using their

1. Fundamental aspects
10 1. Sensor technology: past, present, and future

(A)
SARS-CoV-2
Nitrocellulose strip LFA

(B)
Bare gold

Epitope adsorption Electropolymerization


Template removal

Protein

Epitope 1
Epitope 2
AuNPs Protein capture

FIGURE 1.4 (A) Portable membrane-based virus detection strip [42]; (B) Imprinting
process for generating nanomaterial amplified polyclonal synthetic antibodies [3]. AuNPs,
Gold nanoparticles; LFA, lateral flow assay; SARS-CoV-2, severe acute respiratory corona-
virus 2.

antibody-mimicking properties has been particularly challenging. Lower


affinity, template bleeding, denaturation, and conformational fluctuations
of proteinaceous templates during imprinting, and nonspecific binding
are some of the obstacles that MIP-based protein detection has faced.
However, the integration of novel technologies to molecular imprinting
has led to promising results. Some of these auspicious approaches
include computationally selecting stabile epitopes as templates [36],
imprinting with multiple epitopes to introduce polyclonality [3], incorpo-
ration of conductive or plasmonic nanomaterials to promote signal
response at lower concentrations of the target protein [43], introducing
multifunctionalities via postimprinting modifications [44], spatial confine-
ment of epitopes during imprinting [45] as well as using dual epitope
MIPs in a plasmonic immunosandwich assay [46]. Molecular machines
based on DNA walkers [47] as well as the nucleotide cleavage activity of
CRISPR/Cas (clustered regularly interspaced short palindromic repeats/
CRISPR-associated proteins) [48] effectors are both exciting neoteric
approaches to enhance nucleic acid-mediated biosensing.
In addition to high-affinity receptors, the future of sensor technology
may also include more propitious detection mechanisms. An excellent
example is the use of molecular holography, so-called “molography,” to
circumvent the issue of nonspecific binding in clinical biosensing [49].
Another encouraging strategy for analyte detection is the use of smart-
phones since they offer international connectivity and exhibit enormous
potential for POCT and point-of-need systems. Smartphones can act as

1. Fundamental aspects
1.5 Conclusions and remarks 11

detectors or as instrumental interfaces. Owing to their compatibility across


colorimetric, luminescent, and electrochemical setups, smartphone-based
assays are considered highly versatile and suitable for widespread futuris-
tic applications [50].
The future of biosensing extrapolates the concept of recognition itself
to in vivo events such as pathogen transport and dissemination [51].
Nanomaterial-mediated response amplification may also be harnessed
for high-throughput drug-screening [52]. The advent of in vitro transla-
tion for cell-free protein synthesis has elucidated the synthesis of sensor
arrays relying on the difficult-to-express membrane proteins [53].
Biosensor miniaturization into microfluidic total analysis systems or the
modern lab-on-a-chip and the even more recent organ-on-a-chip may
soon become critical for multiple stages in the process of drug discovery
as well as the development [54]. They can facilitate a better understand-
ing of the pathophysiology of human diseases and organ function.
Implantable, subcutaneous biosensors are tools for continuous monitor-
ing of various metabolites generated in the human body and with rising
interest in artificial organs, such sensors are expected to achieve rapid
progress and commercialization. The development of wearable sensors
is also expected to transform noninvasive analyte quantification, espe-
cially in the area of clinical diagnostics and sports. Due to all these
developments, biosensors are projected to value over USD 40 billion
within the next half-decade [55].

1.5 Conclusions and remarks

Sensor technology in the past revolved around the stimuli-response


behavior between the target and the receptor enzyme. These sensors
were often electrochemical and capable of detecting a singular target.
The targets were themselves small molecules such as blood oxygen,
glucose, lactates, urea, etc. Furthermore, conventional receptors were
sourced from nature and were therefore subjected to complex, expen-
sive, and time-consuming extraction and purification steps. Although
research on synthetic recognition elements was simultaneously under-
way, they were rigid silicon particles with an affinity for small organic
molecules that are irrelevant for clinical, food, or defense purposes.
Though these initial few decades since Clark’s first biosensor laid the
foundation of sensors as we know today, their translation to industrial
mass-production as well as ease of operation for the end-consumer was
extremely limited.
To address these concerns, several emerging concepts were assimi-
lated into sensor technology. The most prominent of these is nanotech-
nology with nanomaterial-based sensors yielding multifold higher

1. Fundamental aspects
12 1. Sensor technology: past, present, and future

sensitivity and specificity with accelerated kinetics in addition to super-


ior control of the sensor design and performance. Computational
modeling is another vital tool that enables the fabrication of sophisti-
cated biosensing systems by allowing in silico optimization thereby
reducing valuable experimental time and research cost. Novel materials
such as aptamers and intelligent MIPs are rapidly replacing conven-
tional receptors owing to their durability, robustness, low cost, and effi-
cient synthesis. Today, interest in vitro methods such as SELEX and
phage display is expanding at an exponential rate.
The global strain on healthcare systems is driving the development of
POCT to ease the burden on centralized laboratories. Inexpensive, ubiqui-
tous, and easy-to-operate platforms such as microfluidic paper assays,
smartphone-mediated detection, wearable sensors, etc., are expected to
lead the future of sensing technology. Intelligent polyclonal synthetic
ligands, as well as DNA molecular machines, are capable of introducing
multifunctionality and even multiple analyte detection. With these prom-
ising developments at the helm, the ultimate future of biosensing is the
precise mimicry of natural recognition events that are tailored according
to the targeted analytes and therefore efficiently discriminate against all
nonspecific interferents while allowing single particle detection.

Acknowledgments
Z.A. thanks the German Research Foundation (DFG, Grant number: 428780268) for the
financial support as the principle investigator.

References
[1] L.C.J. Clark, Monitor and control of blood and tissue oxygen tensions, Trans. Am. Soc.
Artif. Intern. Organs 2 (1956) 41 48.
[2] N. Dolmacı, S. Çete, F. Arslan, A. Yaşar, An amperometric biosensor for fish freshness
detection from xanthine oxidase immobilized in polypyrrole-polyvinylsulphonate
film, Artif. Cells Blood Substitutes Biotechnol. 40 (2012) 275 279. Available from:
https://doi.org/10.3109/10731199.2011.646410.
[3] M. Pirzada, E. Sehit, Z. Altintas, Cancer biomarker detection in human serum samples
using nanoparticle decorated epitope-mediated hybrid MIP, Biosens. Bioelectron. 166
(2020) 112464. Available from: https://doi.org/10.1016/j.bios.2020.112464.
[4] A.P.F. Turner, Biosensors: then and now, Trends Biotechnol. 31 (2013) 119 120.
[5] C.S. Kosack, A.-L. PAge, P.R. Klatser, A guide to aid the selection of diagnostic tests,
Bull. World Health Organ. 95 (2017) 639 645.
[6] M. Pirzada, Z. Altintas, Nanomaterials for healthcare biosensing applications, Sensors
19 (2019) 5311. Available from: https://doi.org/10.3390/s19235311.
[7] R. Birla, Biosensors in tissue and organ fabrication, in: R. Birla (Ed.), Tissue
Engineering for the Heart. Learning Materials in Biosciences, Springer International
Publishing, Cham, 2016, pp. 31 57. ISBN 978-3-319-41504-8.

1. Fundamental aspects
References 13
[8] E. Eltzov, A.L. Cesarea, De, Y.K.A. Low, R.S. Marks, Indoor air pollution and the con-
tribution of biosensors, EuroBiotech J. 3 (2019) 19 31. Available from: https://doi.
org/10.2478/ebtj-2019-0003.
[9] Z. Altintas, I. Chianella, G. Ponte, Da, S. Paulussen, S. Gaeta, et al., Development
of functionalized nanostructured polymeric membranes for water purification,
Chem. Eng. J. 300 (2016) 358 366. Available from: https://doi.org/10.1016/j.
cej.2016.04.121.
[10] M. Cremer, Über die Ursache der elektromotorischen Eigenschaften der Gewebe,
zugleich ein Beitrag zur Lehre von den polyphasischen Elektrolytketten, Z. Biol. 47
(1906) 562.
[11] L.C. Clark Jr., C. Lyons, Electrode systems for continuous monitoring in cardiovascu-
lar surgery, Ann. N. Y. Acad. Sci. 102 (1962) 29 45. Available from: https://doi.org/
10.1111/j.1749-6632.1962.tb13623.x.
[12] M.V. Polyakov, Adsorption properties and structure of silica gel, Zhur. Fiz. Khim 2
(1931) 799 805.
[13] F.H. Dickey, Specific adsorption, J. Phys. Chem. 59 (1955) 695 707. Available from:
https://doi.org/10.1021/j150530a006.
[14] G. Wulff, A. Sarhan, The use of polymers with enzyme-analogous structures for the
resolution of racemates, Angew. Chem. Int. (Ed.) 11 (1972) 341.
[15] G. Vlatakis, L.I. Andersson, R. Müller, K. Mosbach, Drug assay using antibody
mimics made by molecular imprinting, Nature 361 (1993) 645 647.
[16] R.A. Llenado, G.A. Rechnitz, Improved enzyme electrode for amygdalin, Anal.
Chem. 43 (1971) 1457 1461. Available from: https://doi.org/10.1021/ac60305a009.
[17] J.A.-T. Walker, X. Wang, K. Peter, K. Kempe, S.R. Corrie, Dynamic solid-state ultra-
sound contrast agent for monitoring pH fluctuations in vivo, ACS Sens. 5 (2020)
1190 1197. Available from: https://doi.org/10.1021/acssensors.0c00245.
[18] S.J. Updike, G.P. Hicks, The enzyme electrode, Nature 214 (1967) 986 988. Available
from: https://doi.org/10.1038/214986a0.
[19] G.G. Guilbault, J.G. Montalvo, Urea-specific enzyme electrode, J. Am. Chem. Soc. 91
(1969) 2164 2165. Available from: https://doi.org/10.1021/ja01036a083.
[20] E. Von Behring, S. Kitasato, Über das Zustandekommen der Diphtherie-Immunität
and der Tetanus-Immunität bei Thieren, Dtsch. Medizinische Wochenschr. 16 (1890)
1113 1114.
[21] R.J. Goldberg, A theory of antibody—antigen reactions. I. Theory for reactions of
multivalent antigen with bivalent and univalent antibody, J. Am. Chem. Soc. 74
(1952) 5715 5725. Available from: https://doi.org/10.1021/ja01142a045.
[22] R.S. Yalow, S.A. Berson, Assay of plasma insulin in human subjects by immunologi-
cal methods, Nature 184 (1959) 1648 1649. Available from: https://doi.org/10.1038/
1841648b0.
[23] S. Avrameas, J. Uriel, Méthode de marquage d’antigènes et d’anticorps avec des
enzymes et son application en immunodiffusion, C. R. Acad. Sci. Hebd. Seances
Acad. Sci. D. 262 (1966) 2543 2545.
[24] P.K. Nakane, G.B. Pierce, Enzyme-labeled antibodies: preparation and application for
the localization of antigens, J. Histochem. Cytochem. 14 (1966) 929 931. Available
from: https://doi.org/10.1177/14.12.929.
[25] E. Engvall, P. Perlmann, Enzyme-linked immunosorbent assay (ELISA) quantitative
assay of immunoglobulin G, Immunochemistry 8 (1971) 871 874. Available from:
https://doi.org/10.1016/0019-2791(71)90454-X.
[26] G. Köhler, C. Milstein, Continuous cultures of fused cells secreting antibody of pre-
defined specificity, Nature 256 (1975) 495 497. Available from: https://doi.org/
10.1038/256495a0.

1. Fundamental aspects
14 1. Sensor technology: past, present, and future

[27] F. Nasrin, A.D.; Chowdhury, K. Takemura, I. Kozaki, H. Honda, O. Adegoke, et al.,


Fluorometric virus detection platform using quantum dots-gold nanocomposites opti-
mizing the linker length variation, Anal. Chim. Acta 1109 (2020) 148 157. Available
from: https://doi.org/10.1016/j.aca.2020.02.039.
[28] V.M. Generalov, O.V. Naumova, B.I. Fomin, S.A. P’yankov, I.V. Khlistun, A.S.
Safatov, et al., Detection of Ebola virus VP40 protein using a nanowire SOI biosensor,
Optoelectron. Instrum. Data Process. 55 (2019) 618 622. Available from: https://doi.
org/10.3103/S875669901906013X.
[29] M. Pirzada, Z. Altintas, Chapter 14 - Template removal in molecular imprinting:
principles, strategies, and challenges, in: A.B.T.-M.I. Denizli, for N. and O.S.A. (Eds.),
Molecular Imprinting for Nanosensors and Other Sensing Applications, Elsevier,
Amsterdam, 2021, pp. 367 406. ISBN 978-0-12-822117-4.
[30] B.D. Mansuriya, Z. Altintas, Enzyme-free electrochemical nanoimmunosensor based on
graphene quantum dots and gold nanoparticles for cardiac biomarker determination,
Nanomaterials 11 (3) (2021) 578. Available from: https://doi.org/10.3390/nano11030578.
[31] Z. Altintas, A. Guerreiro, S.A. Piletsky, I.E. Tothill, NanoMIP based optical sensor for
pharmaceuticals monitoring, Sens. Actuators B Chem. 213 (2015) 305 313. Available
from: https://doi.org/10.1016/j.snb.2015.02.043.
[32] E.E. May, J.C. Harper, S.M. Brozik, Computational biosensors: molecules, algorithms,
and detection platforms, in: J. Suzuki, T. Nakano, M.J. Moore (Eds.), Modeling,
Methodologies and Tools for Molecular and Nano-scale Communications: Modeling,
Methodologies and Tools, Springer International Publishing, Cham, 2017,
pp. 541 577. ISBN 978-3-319-50688-3.
[33] S. Sivan, S. Tuchman, N. Lotan, A biochemical logic gate using an enzyme and its
inhibitor. Part II: The logic gate, Biosystems 70 (2003) 21 33. Available from:
https://doi.org/10.1016/S0303-2647(03)00039-X.
[34] I.-H. Oh, D.-Y. Park, J.-M. Cha, W.-R. Shin, J.H. Kim, S.C. Kim, et al., Docking simula-
tion and sandwich assay for aptamer-based botulinum neurotoxin type C detection,
Biosensors (2020) 10.
[35] M.L. Simpson, G.S. Sayler, J.T. Fleming, B. Applegate, Whole-cell biocomputing,
Trends Biotechnol. 19 (2001) 317 323. Available from: https://doi.org/10.1016/
S0167-7799(01)01691-2.
[36] Z. Altintas, A. Takiden, T. Utesch, M.A. Mroginski, B. Schmid, F.W. Scheller, et al.,
Integrated approaches toward high-affinity artificial protein binders obtained via
computationally simulated epitopes for protein recognition, Adv. Funct. Mater. 29
(2019) 1 11. Available from: https://doi.org/10.1002/adfm.201807332.
[37] R. Viveiros, K. Karim, S.A. Piletsky, W. Heggie, T. Casimiro, Development of a
molecularly imprinted polymer for a pharmaceutical impurity in supercritical CO2:
rational design using computational approach, J. Clean. Prod. 168 (2017) 1025 1031.
Available from: https://doi.org/10.1016/j.jclepro.2017.09.026.
[38] Z. Altintas, M.J. Abdin, A.M. Tothill, K. Karim, I.E. Tothill, Ultrasensitive detection of
endotoxins using computationally designed nanoMIPs, Anal. Chim. Acta 935 (2016)
239 248. Available from: https://doi.org/10.1016/j.aca.2016.06.013.
[39] C. Tuerk, L. Gold, Systematic evolution of ligands by exponential enrichment: RNA
ligands to bacteriophage T4 DNA polymerase, Science (80-.) 249 (1990) 505 510.
Available from: https://doi.org/10.1126/science.2200121.
[40] A.D.; Ellington, J.W. Szostak, In vitro selection of RNA molecules that bind specific
ligands, Nature 346 (1990) 818 822. Available from: https://doi.org/10.1038/346818a0.
[41] G.P. Smith, Filamentous fusion phage: novel expression vectors that display cloned
antigens on the virion surface, Science (80-.) 228 (1985) 1315 1317. Available from:
https://doi.org/10.1126/science.4001944.

1. Fundamental aspects
References 15
[42] B.D. Grant, C.E. Anderson, J.R. Williford, L.F. Alonzo, V.A. Glukhova, D.S. Boyle,
et al., SARS-CoV-2 coronavirus nucleocapsid antigen-detecting half-strip lateral flow
assay toward the development of point of care tests using commercially available
reagents, Anal. Chem. 92 (2020) 11305 11309. Available from: https://doi.org/
10.1021/acs.analchem.0c01975.
[43] E. Sehit, J. Drzazgowska, D. Buchenau, C. Yesildag, M. Lensen, Z. Altintas,
Ultrasensitive nonenzymatic electrochemical glucose sensor based on gold nanoparti-
cles and molecularly imprinted polymers, Biosens. Bioelectron. 165 (2020) 112432.
Available from: https://doi.org/10.1016/j.bios.2020.112432.
[44] T. Saeki, E. Takano, H. Sunayama, Y. Kamon, R. Horikawa, Y. Kitayama, et al.,
Signalling molecular recognition nanocavities with multiple functional groups pre-
pared by molecular imprinting and sequential post-imprinting modifications for
prostate cancer biomarker glycoprotein detection, J. Mater. Chem. B 8 (2020)
7987 7993. Available from: https://doi.org/10.1039/D0TB00685H.
[45] R. Xing, Y. Ma, Y. Wang, Y. Wen, Z. Liu, Specific recognition of proteins and pep-
tides via controllable oriented surface imprinting of boronate affinity-anchored epi-
topes, Chem. Sci. 10 (2019) 1831 1835. Available from: https://doi.org/10.1039/
c8sc04169e.
[46] R. Xing, Y. Wen, Y. Dong, Y. Wang, Q. Zhang, Z. Liu, Dual molecularly imprinted
polymer-based plasmonic immunosandwich assay for the specific and sensitive
detection of protein biomarkers, Anal. Chem. 91 (2019) 9993 10000. Available from:
https://doi.org/10.1021/acs.analchem.9b01826.
[47] H. Zhang, X. Xu, W. Jiang, An interparticle relatively motional DNA walker and its
sensing application, Chem. Sci. 11 (2020) 7415 7423. Available from: https://doi.
org/10.1039/D0SC00109K.
[48] Y. Liu, H. Xu, C. Liu, L. Peng, H. Khan, L. Cui, et al., CRISPR-Cas13a nanomachine
based simple technology for avian influenza A (H7N9) virus on-site detection, J.
Biomed. Nanotechnol. 15 (2019) 790 798. Available from: https://doi.org/10.1166/
jbn.2019.2742.
[49] V. Gatterdam, A. Frutiger, K.-P. Stengele, D. Heindl, T. Lübbers, J. Vörös, et al., Focal
molography is a new method for the in situ analysis of molecular interactions in bio-
logical samples, Nat. Nanotechnol. 12 (2017) 1089 1095. Available from: https://doi.
org/10.1038/nnano.2017.168.
[50] A. Roda, E. Michelini, M. Zangheri, M. Di Fusco, D. Calabria, P. Simoni,
Smartphone-based biosensors: a critical review and perspectives, TrAC. Trends Anal.
Chem. 79 (2016) 317 325. Available from: https://doi.org/10.1016/j.trac.2015.10.019.
[51] C. Qin, W. Li, Q. Li, W. Yin, X. Zhang, Z. Zhang, et al., Real-time dissection of
dynamic uncoating of individual influenza viruses, Proc. Natl. Acad. Sci. 116 (2019)
2577 2582. Available from: https://doi.org/10.1073/pnas.1812632116.
[52] S.J. Park, J. Kim, J. Kim, S. Kang, H.J. Cha, H.J. Cha, et al., Discovery of direct-acting
antiviral agents with a graphene-based fluorescent nanosensor, Sci. Adv. 6 (2020)
1 12. Available from: https://doi.org/10.1126/sciadv.aaz8201.
[53] F.W. Scheller, A. Yarman, T. Bachmann, T. Hirsch, S. Kubick, R. Renneberg, et al.,
Future of biosensors: a personal view, in: M.B. Gu, H.-S. Kim (Eds.), Biosensors
Based on Aptamers and Enzymes. Advances in Biochemical Engineering/
Biotechnology, vol. 140, Springer, Berlin, Heidelberg, 2013, pp. 1 28.
[54] L.A. Low, C. Mummery, B.R. Berridge, C.P. Austin, D.A. Tagle, Organs-on-chips:
into the next decade, Nat. Rev. Drug Discov. (2020). Available from: https://doi.org/
10.1038/s41573-020-0079-3.
[55] All the Research Global Biosensors Market—Segment analysis, opportunity assess-
ment, competitive intelligence, industry outlook 2016–2026, 2020.

1. Fundamental aspects
C H A P T E R

2
Fundamentals of sensor
technology
Larbi Eddaif1,2 and Abdul Shaban1
1
Research Centre for Natural Sciences, Institute of Materials and
Environmental Chemistry, Budapest, Hungary, 2Óbuda University, Faculty
of Light Industry and Environmental Engineering, Budapest, Hungary

2.1 Sensor, actuator, and transducer fundamentals

2.1.1 Introduction
Components of a detection system typically consist of sensors, actua-
tors, transducers, output display, and electronics. The terms sensors and
transducers are generally related to measurement arrangements where
the sensor is an element that delivers functional output signal as a
response to a quantified substance being sensed. Simply, a sensor is a
device that perceives alterations in a physical stimulus and produces
a measurable analogous output signal that can be evaluated and further
treated [1]. In other terms, a sensor is an electronic device capable of
transforming a physical, chemical, or biological quantity into an electri-
cal one (signal) (e.g., a frequency, a potential, or a current) (Fig. 2.1).
Sensors are composed of many parts, namely: The test body is a sen-
sitive element that transforms the measured magnitude to a measurable
physical quantity. The transducer translates the physical quantity into
an electrical one (output signal). The housing box is a mechanical ele-
ment for protecting, holding, and fixing the sensor. And the packaging/
conditioning electronics are a device that converts the sensor’s output
signal into a standard measurement signal and are the link between the
sensor and the control system since they amplify and process the electri-
cal signal.

Advanced Sensor Technology


DOI: https://doi.org/10.1016/B978-0-323-90222-9.00003-0 17 © 2023 Elsevier Inc. All rights reserved.
18 2. Fundamentals of sensor technology

Physical, Electrical
chemical, or
biological
Sensor quantity
(Signal)
quantity

Test body Transducer Conditioning


electronics

Intermediate Exploitable Housing box


physical quantity physical quantity

FIGURE 2.1 Working principle and different components of a sensor.

Sensors differ from actuators in the sense that an actuator is an ele-


ment that functions in a reversible mechanism to sensors. In other words,
the actuator transforms an electrical output signal into a physical event,
whereas the sensor converts physical results into an electrical output sig-
nal. While sensors are used at the input of a system, actuators are used to
perform output functions in a system as they control an external device.
Transducers are devices that convert energy in one form into another
form. Generally, the energy is in the form of a signal. A transducer is a
term collectively used for both sensors and actuators [1,2].
Selecting an appropriate sensor must fulfill certain criteria, where
certain features must be taken into consideration such as the form of
sensing, working principle, power consumption, precision, environmen-
tal circumstances, price, sensitivity and selectivity, the limit of detection
(LOD) and range, and device calibration. Commonly, sensors are
characterized by metrological parameters that are experimentally
evaluated based on various factors as shown in Table 2.1.
By constructing the calibration curve (Fig. 2.2) of a sensor, it is possi-
ble to determine and understand the relationship between the input and
the output quantities, in terms of metrological parameters and detection
features (sensitivity, detection limit, dynamic and linear ranges, etc.).

2.1.2 Sensor characteristics


Owing to the growing demand for sensors in new applications,
innovative devices for sensor technologies are pursued where new tech-
nologies can offer exceptional impacts like reduced sensor size, low
price, high effectiveness, more stability, and shorter response time [3].
The increasing awareness of important application fields like environmen-
tal contamination, dangerous vapors and fumes, led to the development

1. Fundamental aspects
2.1 Sensor, actuator, and transducer fundamentals 19

TABLE 2.1 Metrological parameters of a sensor.


Characteristic Description
Sensitivity The quotient of the output quantity ΔY and the corresponding input
quantity ΔX: S 5 ΔY=ΔX (Output signal variations/Input signal
variations).

Selectivity The ability of a sensor to detect a target element in the presence of


many others contained in the same medium. The selectivity
translates the sensor’s capability to be insensitive toward elements
that are not the object of the measurement, but which influence
its output.
Saturation The stage when the output signal cannot exceed a maximum value,
regardless of the input value.

Limit of Detection The lowest concentration of an analyte can be detected with an


(LOD) acceptable uncertainty. It is calculated based on the equation:
LOD 5 3σ=Swhere σ and S are, respectively, the standard deviation
and the slope of the calibration curve’s linear range.
Reproducibility The agreement of closeness among the results of the same
magnitude measurements, where individual experiments are carried
out according to different methods, using various instruments, by
several persons, in different laboratories, and after fairly long time
intervals compared to a single measurement duration.
Repeatability The agreement of nearness between successful measurement results
of the same quantity with the same method, by the same person,
with the same measuring instruments, in the same laboratory, and
at fairly short time intervals.
Speed This quality expresses the manner of monitoring input variations
over time.
Influencing The quantities that, when applied, are liable to modify the sensor’s
quantities metrological characteristics. They can be of different origins, such as
mechanical, chemical, thermal, electrical, etc.
Range This specifies the limits of the input in which it can vary.
Accuracy The degree of precision between actual measurement and exact
value (%).
Stability The reproducibility of the sensor for constant input over time.
Response time The speed of alteration in output on a stepwise change in input.
Linearity This is specified in terms of percentage of nonlinearity showing
deviation from ideal situation.
Ruggedness The degree of durability under hard operational circumstances.
Hysteresis The characteristic that a transducer has in being unable to repeat its
functionality dependably when used in the opposite direction of
operation.
Drift The long-term stability of the output without changing the input.

1. Fundamental aspects
20 2. Fundamentals of sensor technology

FIGURE 2.2 Sensor signal calibration curve.

of gas-detection apparatus. Several devices are functional in numerous


industries like biomedical applications, chemical sensing, information stor-
age, etc. [4]. The nanotechnology effect on the development of sensors is
huge, where nanoparticles with predefined composition, grain size, and
shape are assisting the innovative development of sensors and are increas-
ing the list of detectable analytes.
For selecting the appropriate sensor/transducer for any particular
detection arrangement, it is very significant to study its performance
characteristics. Several characteristics must be considered before choos-
ing a transducer such as static and dynamic features. The selective per-
formance properties of sensors and transducers might be classified
under two groups: static and dynamic physical characteristics [5]:
• Static characteristics, which are the established performance standards
through static calibration. The most important static characteristics of
sensors and transducers re listed in Table 2.1.
• Dynamic characteristics, which are extracted from dynamic
measurements in the function of time.
In summary, the static features describe the performance when the
detected quantity is constant, while the dynamic features correspond to
dynamic inputs. The important dynamic features that must be put into
consideration when choosing a sensor transducer are dynamic inaccu-
racy, fidelity, response time, and bandwidth. Generally, both the static
and dynamic characteristics of sensors and transducers define the
effectiveness and indicate how to accept the preferred input signals and
discard undesirable inputs.

1. Fundamental aspects
2.1 Sensor, actuator, and transducer fundamentals 21

2.1.3 Signal processing of sensors


The signal conditioning unit is employed to convert the physical
output signal (nonelectrical) of the sensor to a digital output signal
with an electrical quantity. Applied signal processing units include
A/D converters, amplifiers, filters, rectifiers, and modulators.

2.1.3.1 Signals of sensors and transducers


The physical (analog) signals must be properly prepared before con-
version into a useful digital signal. Sensors necessitate signal condition-
ing before the data acquisition element effectively and precisely receives
the output signal. Signal conditioning consists of electronic circuits that
prepare the measured signal for further processing.
Transduction is attaining energy in one form and converting it into
another one, besides quantifying the energy change or energy input.
Numerous measured signals can be quantified via a variety of transduc-
tion approaches. Transduction principles can be categorized according to
the received and generated energy form of sensor signals [3,6]. According
to their transduction principles, transducers can be classified as:
• Passive transducers: Resistance variation type, capacitance variation
type, inductance variation type, voltage, and current type.
• Active transducers: Photo-voltaic cell, thermopile, moving coil type,
piezoelectric type.
Transducers sense physical phenomena and transform the measur-
and into an electrical signal. However, possibly these signals will not be
in the appropriate forms. Signals given by a transducer could be nonlin-
ear or noisy. Therefore before further conversion, it is crucial to elimi-
nate the noise and nonlinearity related to the output from a sensor or a
transducer. It is also desirable to adjust the amplitude (high/low) to the
desired (analog/digital) form of the produced signals into adequate lim-
its and form. These activities are accomplished by a process designated
as “signal processing.” Signal processing affects the sensor output signal
in numerous ways [6]:
• To guard the sensor elements from any loss due to high current or
voltage signals;
• To transform the output signal from a transducer into the foreseen
form (i.e., voltage/current);
• To amplify/attenuate the signals to a suitable level for the next
process;
• To reduce noise from a signal and improve the S/N ratio;
• And, to manipulate the signal from its nonlinear to a linear form.

1. Fundamental aspects
22 2. Fundamentals of sensor technology

2.1.3.2 Signal conditioning of sensors


Signal conditioning is one of the essential building blocks of up-to-
date data acquisition systems, also known as DAS or DAQ. To perform
physical sensing, the DAS consists of four main modules: sensors, signal
conditioning, an analog-to-digital converter (ADC), and a personal com-
puter with DAQ software for signal logging and analysis. Therefore sig-
nal conditioners receive the analog signal from the sensor, and after
manipulation, the signal is transferred to the ADC subsystem where
digitization and processing take place by specialized software, and then
displayed on liquid crystal display. screens, saved to storage facilities,
examined, and assessed. Signal conditionings require some essential ele-
ments to be useful for data acquisition systems such as electrical isola-
tion, appropriate sensor connection accessories, detection range setup,
signal filtering, and the conformation of sensor requirements.
The most useful signal conditioners offer electrical isolation between
inputs and outputs, which reduces noise, averts ground loops, and
guarantees precise sensing tests.
Modern signal conditioners are completely adjustable to the applied
sensors by employing proper connectors. The capability to pick and set
up the suitable sensing range and signal filtration are very indispens-
able functions in the process of signal conditioning. Practical signal con-
ditioners are requisite to be perfectly adjustable to the intended sensor.
To deliver any useful signal, a sensor output signal needs to be
amplified with an amplifier that has a voltage gain up to 104 and a cur-
rent gain up to 106. The amplification of a linear signal with the output
signal is an exact reproduction of the input, just changed in amplitude,
thus amplification is part of signal conditioning. When using analog
sensors, generally some form of amplification (gain), impedance match-
ing, isolation between the input and output, or perhaps filtering (fre-
quency selection) may be required before the signal can be used; this is
conveniently performed by operational amplifiers.
Also, when measuring very small physical changes, the output signal
of a sensor can become “contaminated” with undesirable signals or
voltages that prevent the required actual signal from being measured
properly. These unwanted signals are called “noise.” This noise or inter-
ference can be either significantly reduced or even eliminated by using
signal conditioning or filtering techniques.
By using either a low pass or a high pass or even a bandpass filter,
the “bandwidth” of the noise can be reduced enormously, and only the
required output signal is left.
Both amplification and filtering play a significant role in interfacing
both sensors and transducers to microprocessor and electronics-based
systems in “real world” conditions. Increasing the signal-to-noise ratio

1. Fundamental aspects
2.2 Sensors’ classification 23

is usually performed by taking several measurements (data) and then


averaging them to obtain the final value.

2.2 Sensors’ classification


As deliberated earlier, a transducer is an element, which translates a
definite measurand into a functional output signal employing a trans-
duction mechanism [2,6]. Another useful definition is: a transducer
is a device that transforms a signal from one form of energy to another.
A transducer consists mainly of two elements:
• Sensing element, which detects and reacts to the physical magnitude.
• Transduction element, which converts the nonelectrical signal into a
proportional electrical one.
Sensors can be classified according to several criteria: (i) primary
measured quantity, (ii) transduction principles, (iii) material and tech-
nology, (iv) property, and (v) applications. Out of these criteria, the
transduction principle is the essential standard of classification. Another
method for classifying sensors is based on the output signals, which is
the stimulus being sensed, and is generally associated with the follow-
ing properties [1,2]:
• Acoustic: Wave characteristics (amplitude, phase polarization),
spectrum, wave velocity, etc.
• Biological/Chemical: pH, the concentration of species in the
environment, additives or constituents in liquid, etc.
• Electrical: Conductivity, voltage, resistance, charge, current,
inductance, etc.
• Optical: Refractive index, reflectivity, polarization, light intensity,
wavelength, etc.
• Magnetic: Magnetic moment, magnetic flux density, etc.
• Mechanical: Strain, stress, torque, flow, length, force, pressure,
acceleration, etc.
• Thermal: Flux, thermal conductivity, heat flow, specific heat,
temperature, etc.
Sensors can also be classified as active or passive. For active sensors, a
power (excitation) signal is needed from an external source. However,
passive sensors directly produce the output signal in response to the
input stimulus. In this contribution, the classification overview includes
the transducers, for active transducers, the input energy is applied as a
control signal in the course of conveying energy from the power source
to a proportional output signal, while in passive transducers, the input
energy is directly converted to the output one.

1. Fundamental aspects
24 2. Fundamentals of sensor technology

2.2.1 Chemical sensors


2.2.1.1 Overview
A chemical sensor is a device that transforms chemical data into a
valuable output signal. Generally, it converts physicochemical proper-
ties or chemical interactions (e.g., concentration or total composition of
specific species into an output signal) [6]. Chemical sensors are consist-
ing of two essential functional parts: the receptor and the transducer. The
transformation of chemical data into an energy form, which can be mea-
sured by the transducer, takes place at the receptor element of the sensor.
The receptor elements of chemical sensors can be classified according to
different operating principles:
• Physical: a physical phenomenon is taking place where no chemical
reaction is involved such as measurement of conductivity,
temperature, or mass variation.
• Chemical: a chemical reaction takes place providing the output signal.
• Biochemical: a biochemical process is a cause behind the analytical
signal.
The report of Scopus data proves that nonstop growth in chemical
sensor-related publications has occurred in the last two decades, reach-
ing B 9070 papers in 2020 (Fig. 2.3). This analysis intensely shows the

FIGURE 2.3 The progressive increase in the number of papers related to chemical sen-
sors from 2001 to 2020 (Scopus database, 3 November 2021, keywords for search: chemical
sensors).

1. Fundamental aspects
2.2 Sensors’ classification 25

TABLE 2.2 Chronological progress of different sensors and materials development.


Sensor development Year References
• Bacterial cellulose nanopaper-based optical sensors 2015 [7]
• Epidermal electronics 2011 [8]
• Microfluidic paper-based analytical devices 2007 [9]

• PCB-based sensor with integrated microfluidics 1997 [10]


• Soft lithography for PDMS microfluidics 1995 [11]
• Development of SU-8
• Mediated enzyme electrode for amperometric biosensors 1984 [12]
• Polysilicon surface micromachinery technology 1982 [13]
• Dry film photoresists development 1968 [14]

• Microtiter plates 1955 [15]


• First positive photoresist 1940 [14]
• First negative photoresist 1935 [14]
• pH glass electrode 1906 [14]
• Photolithography development 1826 [14]
• Litmus paper for pH sensing 1800 [14]

• Pulp papermaking process 105 [14]

significance of studies connected to chemical sensors and proves that


they are trending in the field of sensors. Thus the key historical devel-
opment and discovery of various sensor and biosensor technologies are
presented in Tables 2.2 and 2.3.

2.2.1.2 Types of chemosensors


Chemical sensors may be classified according to the employed trans-
ducer; Fig. 2.4 shows a simple classification of chemosensors based on
the utilized transduction mode.
In general, the widely employed chemosensors are named according
to the involved transduction principle in the recognition application:
optical transduction for optical chemosensors, electrochemical transduc-
tion for electrochemical sensors, or else piezoelectric transduction for
piezoelectric/gravimetric chemosensors:
• Optical chemosensors are based on optical phenomena resulting from
the interaction between the analyte species with the receptor element.
This sensor type can be further divided depending on the type of

1. Fundamental aspects
26 2. Fundamentals of sensor technology

TABLE 2.3 Historical advances in the development of sensor technology and


biotechnology.

Sensor advance Year References


• CRISPR-powered nucleic acid detection 2017 [16]
• “FreeStyleLibre”: Wearable glucose monitoring system 2014 [14]
• Organ-On-a-Chip devices 2010 [17]
• “ripeSense”: Commercial fruit ripeness sensor 2004 [14]
• Digital PCR discovery 1999 [18]

• Molecularly imprinted polymers as antibody mimics 1993 [19]


• Miniaturized total analysis systems 1990 [20]
• Multianalyte immunoassays’ conception 1989 [21]
• Lateral flow technology-pregnancy home test: first time 1988 [14]
• The technique of phase display 1985 [14]
• SPR-based gas and biosensors 1983 [22]

• Wearable heart rate monitor 1982 [14]


• First miniaturized ISFET-pH sensor 1972 [23]
• First glucose biosensor 1962 [24]
• Primary radioimmunoassay 1959 [25]
• Temperature and pressure reading-ingestible capsule 1957 [26]
• Electrical thermostat invention 1883 [14]

• “Davy Lamp”: First gas sensor 1815 [14]


• Barometer discovery 1643 [14]
• Thermometer invention 1612 [14]

optical properties: absorbance, reflectance, luminescence,


fluorescence, refractive index, opto-thermal effect, light scattering.
• Electrochemical sensors are based on transforming the effect of an
electrochemical interaction between an analyte and the receptor at an
electrode into a useful output signal. Further subgroups can be
distinguished: voltammetric sensors, amperometric devices,
potentiometric sensors, and chemically sensitized field-effect transistors.
• Mass-sensitive chemosensors are based on transforming the mass
alteration at a modified surface into an output signal as frequency.
The mass alteration is triggered by the accumulation or loss of the
analyte on the surface. Subgroups of these types of sensors are
piezoelectric and surface acoustic wave sensors.

1. Fundamental aspects
2.2 Sensors’ classification 27

Chemical Sensors

Electrochemical
Piezoelectric

Optical
Surface Acoustic

Conductometric

Potentiometric
Amperometric
Bulk Acoustic

Guided Wave

Impedimetric

Fluorescence
Wave: QCM

Ellipsometry

OWLS
Wave

SPR
FIGURE 2.4 Classification of chemical sensors based on transduction mode.

2.2.2 Biosensors
2.2.2.1 Overview
A biosensor is an analytical instrument that converts a biological pro-
cess into an electrical signal, employing biological elements, including
enzymes, tissues, microorganisms, cells, amino acids, etc., which are
generally attached to a transducer converting the biological information
into an electrical signal (Fig. 2.5).
The choice of transducer depends on the biological reaction taking
place. The most commonly employed material is typically an enzyme,
and one of the frequently utilized feedbacks is the enzyme oxidation
reaction, where the latter is considered as a catalyst directly affecting
the current transport capacity of the enzyme being tested. The output of
the transducer (typically a current) is commonly transformed into a
voltage output signal to be suitably evaluated and presented.

2.2.2.2 Types of biosensors


Biosensors can be categorized into two classes: either related to the
biological recognition element: DNA, enzymes, antibodies, microorganisms,
tissues, cell receptors, etc. Or related to the transduction principle: optical,
electrochemical, and mass-based biosensors:
• Optical biosensors permit the detection of target elements centered on
light phenomena as absorption, scattering, or fluorescence, as a result

1. Fundamental aspects
28 2. Fundamentals of sensor technology

FIGURE 2.5 Working principle and different components of a biosensor.

of interactions between the elements to be detected and the


recognition layer at the sensor’s surface [27]. A focal advantage of
optical biosensors is their nonelectrical nature, providing the ability
to sense multiple elements only by varying the light’s wavelength.
• Electrochemical biosensors, based on the electrochemical interaction
between the sensing biomaterial at the sensor’s surface and the
species to be detected, yielding to an electrical signal, employ
numerous transduction principles, such as potentiometric,
impedimetric, voltammetric, and amperometric transducers.
• Acoustic biosensors, or piezoelectric biosensors, are a subgroup of mass
biosensors. They are based on the frequency shifts at different
overtones when the biological sensing platform is immobilized onto
the biosensor’s surface (usually Au). The biosensor then transforms
the mechanical vibrations related to the detection of target elements
into proportional electrical signals (mass to frequency).

2.2.3 Electrochemical sensors


2.2.3.1 Overview
The growing concern to limit the contamination of air, water, soil,
and food products, besides making biomedical analyzes more reliable,
has created a need for the development of rapid, sensitive, and safe pro-
cesses for detecting various chemical and biological pollutants [28,29].
Electrochemical sensors can provide inexpensive and sensitive tools
based on portable devices capable of rapidly detecting a set of analytes
along with decent sensing characteristics [30].

1. Fundamental aspects
2.2 Sensors’ classification 29

Recently, electrochemical sensors have been making a huge impact


on multiple fields, including drug monitoring [31], early diagnosis of
diseases [32], precise and fast environmental pollutants’ recognition and
quantification [3335], etc., and have been the subject of a great deal of
research and development to provide simple, reliable, and low-cost sys-
tems via experiencing considerable emergence owing to their simplicity
and portability, allowing the transformation of an electrochemical signal
into an exploitable in situ electrical signal related to the target element’s
quantification, making them better alternatives to rather complicated
traditional analytical techniques [34].

2.2.3.2 Types of electrochemical sensors


The fundamentals of electrochemical sensors lie in the mechanism of
transforming the electrochemical interaction happening between the tar-
get analyte and the electrode into an exploitable electrical signal [31],
which is based on the fact that electroactive molecules in solution
exchange electrons with the electrode surface depending on the poten-
tial at which this exchange takes place; the electrochemical transduction
remains the most widely used in electroanalysis and biosensing applica-
tions thanks to its simplicity, low cost, and rapidity of response [36].
Electrochemical sensors can be classified as follows:
• Amperometric electrochemical sensors: During a redox reaction,
amperometric transducers measure the generated current at the
working electrode at a constant potential; the current value is
proportional to the analyte’s concentration in solution. Amperometric
transducers are well-known for their wide linear ranges and high
sensitivities compared to potentiometric ones [28].
• Potentiometric electrochemical sensors: Based on measuring the potential
difference between a working electrode under zero current intensity
and a constant potential reference electrode, the measured potentials
are proportional to the analyte’s concentration in solution.
Potentiometric sensors are generally known as ion selective
electrodes (i.e., pH electrodes) [37,38].
• Conductometric electrochemical sensors: The conductivity of a medium is
linearly related to the nature of ions in solution, their charge,
mobility, and concentration. Conductometric sensors are based on the
measurement of conductometric properties between two electrodes
under an alternating current system [30].
• Voltammetric electrochemical sensors: Voltammetric transduction is
based on the measurement of the current flow resulting from the
analytes’ redox reactions in solution under a controlled variation of a
potential difference between the reference and the working
electrodes. The applied potential varies as a function of time and the

1. Fundamental aspects
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only a long monotonous buzz of unmeaning words, and when the
verdict was pronounced, he did not know whether it was more or
less severe than he had expected.
He was acquitted of the charge of wilful murder, but found guilty of
homicide, and sentenced to five years’ penal servitude.
George repeated the words to himself, trying to realise them. But
all he knew was that he was thankful the trial was over.
CHAPTER XXIX.
It is well for the wounded spirit when the body falls sick in
sympathy, and the piercing thoughts become blunted into vague
fancies, and the heavy load of doubt and despair falls off with the
responsibilities of sane and sound existence.
George Lauriston, who had been unconsciously sickening ever
since the day when he was arrested, and, stupefied by misery, had
gone off to prison in clothes which had been saturated with the rain,
was, on the day after his conviction, too ill to stand; his skin was hot
and dry, his eyes were glazed and dull, and his limbs racked with
pains. The surgeon, on being sent for to see him, ordered his
immediate removal to the hospital, where for three weeks he was
laid up with a sharp attack of rheumatic fever. He recovered very
slowly, but as this is a common case with sick prisoners, who not
unnaturally prefer the relaxed discipline and better food of the
hospital ward to the monotonous life and meagre fare which awaits
them on their convalescence, he received no special attention on
that account, and as soon as he was declared fit to be removed, he
was consigned to Toulon with a batch of other convicts destined, like
himself, for work in the dockyards. He was visited in his illness by
Ella Millard, but he was unable either to recognise her, or to learn
from her lips the painful tidings that every effort to find his wife had
proved fruitless. He started on his miserable journey, therefore,
without one parting word to cherish during the long months which
must elapse before he could see a friend’s face again, and knowing
nothing of the efforts that were being made on his behalf.
The New World energy which poor little Lady Millard had used
only to force herself into the same mould as her husband’s less
vivacious compatriots, had blossomed out in her youngest daughter
to a quality of the highest order, capable, on occasion, of
transforming the plain, unobtrusive girl into something like a heroine.
Ella was convinced that the sentence passed upon George Lauriston
was unduly severe, and further, that if carried out it would kill him;
therefore she put forth all her powers of perseverance and resource
in the endeavour to get it mitigated. To her uncle, Lord
Florencecourt, and her aunt Lady Crediton, both of whom were
persons of influence, she did not allow one moment’s rest until,
through the English ambassador at Paris, she had obtained a
hearing of the French Minister of the Interior. In this, however, she
did not succeed until the following spring, by which time her poor
friend’s release by surer means seemed to be drawing near.
Before the winter was more than half through George believed that
he was dying. The authorities of the prison thought so too, and out of
compassion for the “bel Anglais,” whose athletic form, distinction of
movement and manner, and the old thoroughness and absorption
with which he did whatever work he had to do, had gained him the
same sort of reputation among the lowest of mankind that he had
formerly held among the highest, they shortened the preliminary
term of confinement within the walls, and put him with the workers in
the dockyard, in the hope that the open air, nipping and keen as it
was in these winter days, might restore the failing vigour of his
frame, and check a hacking cough which made even the warders
shrug their shoulders and mutter “pauvre diable!” as they walked up
and down the echoing stone corridors in the frosty nights of the early
year.
March had come, with bitter winds and no sign of the winter’s
breaking, when George Lauriston was sent, as one of a small gang
of convicts, to repair a breach in the harbour made during a storm
the day before. There was some hard and hazardous work involved,
a portion of the structure having been rendered unsafe by the tearing
away, by the action of the waves, of the outer piles placed to break
their force. Glad of the excitement, however, and of the nearer
approach to their kind of the outer world which the walk to and from
the harbour afforded, the gang of convicts, picked out of the smartest
and best-conducted men, went to this novel work with more alacrity
than usual. The weather was still rough; the waves, of a troubled
greenish-brown colour, were crested with white, and the wind drove
the drizzling sleet straight from the north.
In spite of the fierce gusts of wind, of the clouds of saturating
spray which broke up against the wall of the harbour and fell with a
patter and a hiss on to the stone, on the first day that the convicts
worked there, a small, slender woman, poorly dressed, who fought
the wind with difficulty and caught her breath with deep-drawn,
struggling sobs as if the exertion hurt her, crept slowly along the
outer side of the slippery pier through the dense sea-showers, until
she was within a few feet of the warder who walked, with fixed
bayonet, up and down, guarding the convicts on the land side. The
warder stopped, and asked her rather brusquely what she wanted.
“Nothing; I only want to get as near as I can to the sea. It’s good
for me,” she answered fluently, but in a foreigner’s French.
And as she looked ill enough for every breath she drew to be
already numbered, and fixed her eyes yearningly on the horizon as if
no nearer object was of moment to her, he let her stay. But each time
that his back was turned on his walk she was up like a hare, in spite
of her evident weakness, eagerly scanning the workers in their
coarse grey uniforms, searching, searching, until at last, at her third
scrutiny, she discovered the man she wanted. It was George
Lauriston. He was working with a will, pickaxe in hand, his feet now
in, now out of the water, his back towards her, his arms rising at
regular intervals, as he dealt blow after blow at the solid masonry.
She did not cry out as she recognised him; she did not even try to
attract his attention; but fell back into her former position and
retained it unchanged through two or three turns and returns of the
warder up and down. The one glance had intoxicated her; she
doubted her own powers of self-restraint, that gave her the blessed
privilege of seeing him, her own husband, in the flesh, after those
long dark months of absence when he had come to her only in
dreams.
After a little while she noted, sitting crouched under the wall, out of
sight of the convicts, that the blows of the pickaxe had ceased. If for
a few moments he was resting, he might, if God would be kind, turn
this way, see her, meet her gaze with his, give her one short kiss of
the eyes that she might carry home and nurse in her memory
through the long nights when she lay awake thinking of him. She
waited, scarcely drawing breath, till the warder turned again. She
had ten full seconds for her venture. Scudding over the great stones
like a lapwing she reached the breach again, and looked over. A cry
rose from her heart, but she stifled it as, through spray, rain, mist, the
wind-driven rain cutting her tender face like stones, the waves
shooting up great geysers of white foam close to her, she met the
look that through long weeks of illness she had hungered for.
“Nouna!” cried George, with a hoarse shout that the waves
drowned with their thunder.
Finger on lip she sped back in a moment, leaving him dazed,
stupefied, half believing, half hoping the figure he had seen was only
a vision of his imagination. For could that little pinched, wasted face,
in which the great brown eyes stood out weirdly, be the bonny bride
whose beauty had seemed to him almost supernatural? He set to
work again mechanically, hardly knowing what he did; but when the
short day began to draw in, and a veil of inky clouds to bring a
shroud-like shadow over the sea, and the warders gave the word to
cease work and muster for the march back to the prison, he saw the
little weird face again, read the short sad message of unwavering
love and weary longing in her great passion-bright eyes, and
resisting, with one supreme effort of the old soldierly habit of
discipline, the dangerous temptation to risk everything and break the
ranks for an embrace, which his failing health told him would
certainly be the last, he marched on with the rest, and left her to
creep—benumbed with cold and wet to the skin, but feverishly happy
in the knowledge that she had seen him again—back to her home to
live on the hope of another such meagre meeting.
The next day was wild, stormy, and bitterly cold, with a driving
north-east wind, and intermittent snow-showers. But when the
convicts were marched down to the harbour, Nouna was already
there, crouching—a small, inert bundle of grey waterproof—under
the shelter of a pile of huge stones, watching for her husband’s
coming with hungry eyes. When the tramp, tramp, upon the flags told
her the gang was approaching she peeped out cautiously, and then,
afraid lest in her desire to escape the notice of any one but George,
she should escape his also, she rose, crept out a few paces from her
shelter, and turned her face boldly towards the advancing men.
George was in the front rank to-day; in the morning light, which beat
full upon his face, she saw him well, saw a terrible change in him;
even while he, on his side, noted more fully the transformation in the
little fairy princess who had taken his whole nature by storm less
than a year ago—from a lovely unthinking child into a sick and
desolate woman. How could he think, as he looked at her, that there
was anything but loss in a change which rent his very heart, and
moved him as no allurement of her beauty, no wile of her sensuous
coquetry had ever done? In spite of the educational enthusiasm he
had spent upon his sixteen-year-old bride, in spite of his genuine
anxiety to surround her with elevating and spiritualising influences, it
thus happened that when at last the spirit instead of the senses
shone out of her yearning eyes, it gave him no gladness, but rather a
deep regret, and instead of thanking heaven for waking the soul he
had in vain longed to reach, he cursed his own fate that he had
brought about this change in the woman for whom he was at all
times ready to die.
He did not pass very near to her, for the little creature was cowed
and shy, afraid of bringing some punishment upon him by any sign of
intelligence. He tried to speak to her, tried to tell her not to wait there,
exposed to the bitter wind and the lightly falling snow; but his voice
was hoarse and broken, nothing escaped his lips but guttural
sounds, which did not even reach her ears. So that when, after a
couple of hours’ work upon the rough stones of the pier, he again
came in sight of his wife, crouching in the same place, watching
patiently for another brief sight of him, he took, to save her from the
risks her fragile frame was running, a resolve, the execution of which
cut him like a knife. He went up to the warder and said:
“That is my wife. She will die of cold if she stays. Please speak to
her gently.”
George saw, as he turned to go back to his work, the poor child’s
white frightened face as the warder addressed her. Slowly, with one
long straining gaze, as if she would draw her loved one into her arms
by the passionate force of her yearning eyes, she turned, and
George saw her hurry away down the pier as fast as her chilled
limbs would let her: and he felt that the little retreating figure which
soon became a mere speck against grey sky, grey sea, grey stone,
had carried away the last shred of human hope and human feeling
that prison life and failing health had left in his breast.
Next day, which was the last of the work in the harbour, Nouna
was not on the pier; but as George took his place with the rest he
found, roughly cut with a knife or some other sharp instrument in one
of the large stones, the letters filled in with red chalk, these words:
“I have been quite good all the time. Good-bye. N.”
It was his wife’s last message to him. George knelt down and put
his lips upon the stone. He had forgotten that he was not alone, but if
he had remembered, it would have made no difference. The waves
might wear out next tide the feebly scrawled marks which perhaps
no eye but his could decipher, or the words might be read by every
man, woman and child in the town—it was all the same to him now;
they were engraved upon his own heart, a complete, a holy answer
to every doubt which had ever troubled him, to every aspiration he
had ever had for the young life he had bound to his own. Love and
sorrow had sanctified her; there was no danger for his darling now.
The man, on the other hand, had only his worst feelings intensified
by misfortune which he could not but look upon as unmerited.
George’s love for his wife remained as strong as ever, but it was now
the one soft spot in a nature rapidly hardening under the influence of
a struggle with fortune in which he had been signally worsted. In the
long hours of the night, when his cough kept him awake even though
he was tired out by a hard day’s labour, he brooded over the wrongs
he had suffered, until the canker of disappointment ate into his heart
and bred there a burning, murderous wish for revenge: not upon the
French law which had condemned him, as he maintained, unjustly—
that was impersonal, intangible, a windmill to fight; not upon the
Colonel, who had faltered in his friendship; not upon Chloris, whose
mischievous caprice had set in motion the force which had indirectly
destroyed him; but a man’s indignant righteous revenge upon the
rascal who had tried from his very wedding-day to come between
him and his wife. George began to feel that it was even more for the
sake of finding Rahas than of meeting Nouna again that he yearned
with a sick man’s longing to live until the time of his release, and
prayed for strength to drag on an existence which with its
hopelessness and its morbid cravings for the savage excitement of
vengeance, was an infernal torment which told, by its intensity, on
his waning strength.
The prison authorities noticed the change in him, and treated him
with what little consideration was possible. The old priest, in
particular, stirred by the fact that “number 42” was a heretic into
giving him something better than the conventional doses of religious
advice which he administered to the devotees of “the true Church,”
proved a most kind friend to him, and it was with a manner of sincere
and warm sympathy that the good father while paying him his usual
visit one day in April, let fall at parting a mysterious whisper about
good news and good friends who had not forgotten him. The
brooding prisoner hardly heeded him. But next morning he was
brought up before the governor, and a paper was formally read out to
him, in which he was informed that the Minister of the Interior, on
having brought under his notice the case of the Englishman, George
Lauriston, now undergoing a sentence of penal servitude at Toulon,
had come to the conclusion that the said sentence was unduly
severe, and that, as the evidence went to show that the crime was
unpremeditated, and committed under strong provocation, a short
term of imprisonment would have been adequate punishment, and
that, in view of the fact that the said George Lauriston had been
already at Toulon working as a convict for nearly four months, the
Minister had decided to remit the remainder of the allotted term of
imprisonment. George listened, but he hardly understood; the
governor, in a few kindly words, then told him that he was a free
man, that he could go back to his friends.
“Friends!” echoed George in a dull voice.
“Come, you cannot deny that you have friends; it is to some of
them that you owe the good news you have just received,” said the
governor. “I understand they are in the town waiting to meet you. Sir
Henry—something I do not recollect, is the name of the gentleman;
and the lady——”
A light broke over George’s face; he spoke some broken words of
thanks in a more human voice.
That evening he was a free man, and was holding, dazed and
trembling as with palsy, on one side the hand of Sir Henry Millard, on
the other that of his daughter Ella.
CHAPTER XXX.
George had not known until this meeting with his old friends how
much ill-health and confinement had pulled him down. He scarcely
dared to look at Ella, for there came a lump in his throat whenever
his eyes fell on her brave, steadfast face. Sir Henry’s presence was
a great relief to them both. The baronet’s comments on the situation
was so inapposite, and he had such a strong sense that he was
rendered ridiculous by this journey to France to chaperon his
daughter in her efforts on behalf of another woman’s husband, that
he gave them something to laugh at when they were only too ready
to cry. Ella was as practical as ever.
“What are you going to do?” asked she, drawing George aside
with her usual brusquerie when the first greetings were over.
“I am going to find Nouna,” said he. “She has been here, and she
went away ill a fortnight ago; I have found that out, and that her black
servant Sundran was with her. I must start to-night.”
“You are too ill for the journey.”
“I am too ill to stay here. I have some work to do in England
besides.”
“What work?”
He did not answer, and there was a pause, during which she
considered him attentively.
“George,” she said at last in a low voice, “you are changed. You
have lost the ‘good’ look you used to have. The work you speak of is
something unworthy of you.”
“It must be something very degrading then; you forget I am a——”
She stopped him imperatively.
“You are my ideal of an Englishman, as honest as any and not so
stupid as some. If you hadn’t been unlucky, I should never have told
you so, but now that you know what a surpassingly lofty opinion I
have of you, I expect you to live up to it.”
“You must let me be human though.”
“That depends. There is good and bad humanity. What do you
want to do?”
“I want to—well—I want to—get at that scoundrel Rahas!”
“You may—on one condition.”
“Well?”
“You musn’t lay a hand on him until you have seen Nouna.”
George looked at her wonderingly.
“Tell me why you make that condition.”
Her answer came at once in a full, deep, steady voice, that
betrayed even more than her words did.
“Because I know that the sight of a face one loves and has longed
to see can extinguish all hatred and anger, everything but happiness;
just as your coming to-night has calmed down all my wicked feelings
towards my uncle and towards—your poor little wife. I can forgive
you for marrying her now—for the first time.”
George was thunderstruck. All the passionate intensity with which
the small, plain girl had loved him and longed for his success in life,
had compassionated him and worked to retrieve his errors, blazed in
her black eyes and seemed to cast a glow over her sallow face. Men
are so much accustomed by reason and experience to associate
women’s fragility of frame with frivolity of mind, that any sudden
discovery of devoted singleness of purpose in one of the soft and
foolish sex strikes them into as much distant awe and reverent
worshipfulness as a manifestation of godhead in the flesh would do.
So that George remained quite silent before Ella, with no inclination
to thank her, but a strong impulse to fall on his knees.
After nearly a minute’s silence, she said, in the same deep voice:
“Will you promise me to see her first?”
George looked at her in a sidelong, shamefaced way.
“I will promise anything in the world you like,” he said huskily.
She smiled happily, and taking his hand, made him sit down
beside her. The joy of having procured his release had thrown her
this evening into an exaltation of feeling which banished her usual
awkwardness, and made her unreserved as only a shy person
unusually moved can be.
“Remember,” she said, “you have to save yourself up for a
journey.” And she turned upon him the motherly look which shines
out in the tenderness of all the best women.
Ella was perfectly happy this evening, and had not an atom of
jealousy that the thoughts of the man, in whose interest she could
forget all scruples of prudery, were bent on another woman. She had
done for him what his wife could not do; there was pride enough in
that knowledge. There had been from the first so little selfishness in
her love that by this time there was none—a not uncommon beauty
of character in the plain of person who, expecting nothing, are more
than content with a little. So she arranged all the details of the
journey, and within a couple of hours she and her father and George
were on their way back to England.
They did not reach London until the second morning after their
departure from Toulon. George was disgusted and alarmed to find
that he could scarcely stand; but he resisted the suggestion that he
should take a day’s rest, being afraid that if he once yielded to his
bodily weakness, it would be a long time before he was able to get
about again. So he left Ella and her father at the hotel where they put
up, and drove to Mary Street to learn whether Rahas still lived there.
This step he took with Ella’s full knowledge; he should fulfil his
promise, he told her, and keep his hands off the Oriental merchant
until after he had found Nouna; but he must set about his search in
his own way.
No. 36, Mary Street looked the same as ever, except that, during
the eleven months which had passed since George first drove up to
the door and dashing up the dingy staircase came suddenly upon an
Arabian Nights’ nook in murky London, the lower windows had
acquired a thicker coating of grime, and the board with the names
“Rahas and Fanah” had lost its freshness of new paint; the brass
vases and lanterns, the Arabian gun, the inlaid table, the Indian
figures were still there, and the fact that the firm did not depend upon
the chance custom of passers-by was more patent than ever.
George stumbled as he got out of the hansom, and felt, almost
without seeing, for the bell. Fatigue, weakness, and the
sleeplessness caused by intense excitement had preyed upon his
body and stimulated his imagination till on this, the first day of his
return to his own country, he was like a man walking in his sleep,
and saw faces and heard voices invisible and inaudible to all but
him. Nouna, as he saw her first, sleeping like a fairy princess, amidst
gorgeous surroundings; the strange doctor, whose warning against
the girl’s dangerous charms rang again in his ears; the dark-faced
Rahas and his pretensions to occult powers—all these recollections
chasing each other through his feverishly excited mind, dulled his
faculties to the cold reality of present experience, and when the door
was opened by a woman whose face was unknown to him, he stood
before her stupidly, without realising that it was he who had
summoned her. When she asked him what he wanted, he pulled
himself together, and asked if Rahas, the merchant, still lived there.
“Yes, he lives here, but he ain’t here to-day; he’s gone to
Plymouth, and won’t be home for a week or so. You can see the old
gentleman if you like, or letters are sent to him.”
Plymouth! The name sent an old suggestion into George’s mind.
He suddenly remembered that Miss Glass, the old servant of his
family who had given Nouna shelter between her leaving Mary Street
and her wedding-day, came from Plymouth, where her parents had
kept a lodging-house. He had never doubted that he should find
Nouna easily, and now he knew in a moment, without further
reasoning, that she was at Plymouth, and that Rahas had gone
down to see her there. So sure did he feel, that he did not even call
at Miss Glass’s house in Filborough Road to make inquiries; but
obtaining from the servant at No. 36 the final information that Rahas
had not long started, George jumped hastily back into his hansom
and drove to Paddington. He found he had just missed the 11.45
train, and there was not another till three o’clock; so he drove to
Waterloo, and learning that there was a train at 2.30, he resolved to
go by that in order to be on the road as soon as possible, although it
arrived no earlier than the three o’clock express from Paddington.
This left him time to go back to the Charing Cross Hotel to say good-
bye to his friends.
Whether she was frightened by the thought of a possible collision
between George in his weakness and the unprincipled Arabian, or
whether she was stung by a feeling of jealousy that the time of her
generous devotion to him was over, her work done, Ella grew ghastly
pale on hearing of his intended journey, and tried to dissuade him
from it. When she found him immovable, she endeavoured to induce
her father to go with him; but both the men laughed this suggestion
to scorn, and the most she could obtain was permission for her and
her father to see him off at the station.
George was absorbed, as he stood at the window of the
compartment in which he was to travel, by a strong feeling of
gratitude towards the young girl on the platform below him, in whose
eyes he read a steady, unwavering friendship and affection, free
from the advancing and receding tide of passion, without coquetry,
without caprice, the noblest love a human creature can give, the one
also which in either sex is sure never to have an adequate return.
George looked down at her pale face reverently, and tried to find
some words to express the overflowing feelings inspired by her
goodness to him; but she would not hear. Stepping back from the
carriage-door with a blush, she affected to interest herself in the rest
of the passengers, when suddenly the flush died away from her face,
and she came hastily back. Looking up at George with an expression
of strong anxiety, she said in a whisper:
“George, for Heaven’s sake be careful; I believe the man himself is
in the next carriage!”
Lauriston, much startled, his face lighting up, tried to open the
door: but she stopped him, saying: “Remember—your promise!”
The next moment the train had started, and George, overcome by
the rush of feelings evoked by the thought that the man whom he
hated was so near to him, sank down into his corner seat in the wet
white heat which strong excitement causes to the bodily weak. He
hoped that Rahas, if indeed it was he whom Ella had seen, had not
caught sight of him; in that case George was sure that he had only to
follow the wily Arabian to be taken straight to the house where
Nouna was. The journey seemed endless; he fell from time to time
into fits of stupor, in which he heard the tramp of the warder through
the rattle of the train, and Nouna calling to him in hoarse, broken
accents unlike her own, and a rasping voice shrieking out to the beat
of the wheels: “Never to meet! Never to meet!” With a start he would
find that prison-walls and darkness had melted back into the
cushioned carriage and the light of day, and remember in a vague,
half-incredulous way that he was on his way to Nouna. Then the
train would stop at a station, and he would look out eagerly, furtively,
scanning the passengers who got out, searching for the man he
wanted. At last, at Salisbury, where the train waited a quarter of an
hour, his anxiety was set at rest. Wrapped in a long overcoat, and
wearing a travelling-cap pulled low over his eyes, Rahas descended
to the platform, walked two or three times up and down with his eyes
on the ground as if in deep thought, and got in again without having
given one glance at any of the other compartments. George had felt
pretty safe from recognition, as he was much altered by illness and
the loss of his moustache, and as, moreover, he was believed to be
still a prisoner in France. Now he was altogether sure that Rahas
was off his guard, and the knowledge gave him confidence. When,
therefore, the Oriental merchant left the train at a little station a few
miles from Plymouth, George only allowed him time to get through
the door before he jumped out after him, and turning up his coat-
collar, as the coolness of the evening gave him an excuse for doing,
gave up his ticket and followed.
Once out of the station, Rahas, without a glance behind him,
struck straight across the fields by a narrow path that led to the
distant light of what George supposed must be some little village. It
was half-past eight; the showers of an April day had saturated the
grass, and a thick damp mist lingered among the trees, most of
which as yet had but a thin spring covering. The moon had not yet
risen, and George had to hurry after Rahas, fearing in the obscurity
to lose sight of him altogether. The numbness which had seized his
tired faculties from time to time on the railway journey now again
began to creep over him, so that the surprise he would at another
time have felt, the questions he would have asked himself as to the
merchant’s leaving the train before he came to Plymouth, now
merged into a dull confusion of ideas, the most prominent of which
was that Rahas was trying to escape him. As the path descended
into a little valley dark with trees, and the figure before him, now
indistinct against the dark background, disappeared over a stile into
the shadows of the copse beyond, this fancy grew stronger and,
feeling that his limbs were unsteady with ever-increasing fatigue,
which made him hot and wet from head to foot, he broke into a run,
reached the stile in his turn, got over it, and stumbling over some
unseen obstacle, slipped on the soft, muddy earth, and fell to the
ground. The next moment he felt himself seized as he lay on his
face, bound with a stout cord that cut into his flesh in his struggles to
free himself, and then dragged through brambles and wet grass into
the little wood. This last was a slow operation, for George was a big
man, and though no longer in the full vigour of his health, he was too
heavy for his dead weight to be pulled along with ease. He lay quite
still, without uttering a sound, recognising, after a valiant but vain
attempt to get free, that he was quite at the mercy of his assailant,
he decided that entire passivity was his best chance of escaping
such a quieting as would save him all further exertion. The first result
of this was that Rahas, when he had continued his slow and tedious
progress with his victim for what seemed a long time, stopped and
peered into his face closely enough for George to make quite sure of
his identity. To his surprise, the Oriental seemed quite relieved to find
that he was not dead.
“Ah ha, you know me,” he muttered, as he encountered the
shining of living eyes in the gloom. “You are not hurt. That is all right.
I do not want to hurt you, be sure of that. I bear you no ill-will.”
“Thank you,” said George quietly. “That is satisfactory as far as it
goes; but I should like to know whether this is the manner in which
you treat chance acquaintances, for example.”
“No,” answered Rahas, quite simply; “I am forced to this last
means of keeping you from the woman whom Heaven, as the
planets declare, has given to me, and whom you have ruined by
instilling into her your own soul, which is killing her fair body day by
day. Do you understand? Her mother has given her to me, is only
waiting for me to take her away to give her the dower you, in your
proud folly, refused. I have waited long, I have tried many ways, to
get what Allah intended for me. Nouna herself, weary of waiting,
dying by inches, has at last given me permission to see her. Must I,
at the last, with success in my very grasp after a year of waiting, see
it wrung from me by the man whose touch has been fatal to this fair
flower of the East? No. The will of Allah must be done. There are
women enough in the world for you; there is only one for me. Nouna
must come to my arms to-night; and for you, after to-night, I am at
your disposal in any way you please.”
There was a strange mixture of cupidity, fanaticism and ferocious
courage in his speech and manner which struck horror into George’s
heart, at the thought that his wife might to-night have to come face to
face, without a husband’s protection, with this man. He uttered a
loud shout and made a sudden effort to rise, which the Arabian
frustrated with a movement as nimble as a hare’s, accompanied by a
short laugh.
“Keep still,” he said more harshly, “and keep your shouting until I
am out of earshot.”
He made no threat in words, but his tone was so significant that
George, to whom danger had restored his full faculties, resolved to
save up his lungs. In a business-like manner Rahas then, with his
knee on the young man’s chest, assured himself that the cord which
bound him was secure, and with a civil and dispassionate “good-
night,” to which the Englishman was in no humour to respond, he
turned and walked rapidly away; his steps scarcely sounded on the
soft, damp earth, and only the crackle of dead branches and the
rustle of living ones, growing fainter and fainter until the sounds
faded quite away, told George that he was retreating rapidly.
Then came a time for the poor fellow when he prayed for death at
last. With the rotting leaves of the previous autumn forming a slimy
pillow for his head, his body sinking slowly into the damp earth, while
a rising wind moaned a low dirge among the surrounding hills and
swept over the thinly-leaved branches above his head with a
sepulchral “hush!” he felt all the horrors of the grave, all its
loneliness, all its impotence, without the one blessing—peace, which
we hope for there in spite of the clergy, who are ferocious as regards
the next world to counter-balance their meekness in this. The deft
Rahas had bound him sailor-fashion, beginning with the middle of
the rope; and the knots were immovable as iron; he began to feel
cramped and benumbed by the cold, the rising moisture amid the
undergrowth of the wood, and the impeded circulation of his blood.
Still his head remained hot as fire, his brain reeling in a mad dance
of fantastic tortures, until at last frenzy came, and pictures of the past
chased each other through his memory, but with a lurid light of horror
upon them which distorted his fairest recollections, and turned them
into ugly nightmares. Then in turn the pictures faded and his senses
began to grow dull, and strange cries to sound in his ears to which
he tried to reply; but his voice would not come, and even as his lips
moved in this effort, the last gleam of sense left him, and he fell into
unconsciousness.
As upon the blackness of night the fair, pure dawn comes
gradually, so George, from the stupor of a deadly lethargy, woke by
slow degrees to sensations of warmth, and light, and joy; and
feeling, before the sense of sight came back to him, a soft touch on
his flesh that set him quivering, and a breath against his lips that
exhaled the very perfume of love, he fancied in the first moments of
a still feebly moving brain, that his prayer had been granted, that he
was dead, and in Heaven. Until suddenly there burst upon his ears a
wild, joyous cry: “He is breathing! He has come back to me—back,
thank God! thank God!”
And his heart leapt up, and an ember of the old fire warmed his
veins. Opening his eyes, which were blinded and dazzled still, he
whispered huskily, “Nouna, my little wife!” and groped about with
weak, trembling arms until she came to him, and lying down by his
side, pressed her lips to his with warm, clinging kisses that carried a
world of loyalty and love straight from her soul to his. Then, while he
felt her soft mouth strained against his, he knew, all dazed and half
benumbed as he still was, that a change had come upon her. It was
not the restless butterfly kiss of a passionate caprice that she gave
him, as in the old days when she would fly from his knee to the
window and back again half a dozen times in five minutes; it was not
the embrace of sincere but timid affection she had learnt to give him
when they lived their struggling life in Paris; it was the seal of patient
and faithful love satisfied at last. From that moment he had no
questions to ask, no explanations to hear. What did it matter where
he was, how he came there, how she came there? But Nouna,
drawing her head back to look at him, saw his lips move, and she
watched them and listened, holding her breath, to his weak whisper:
“Cold, darkness, pain, and the long windy nights—all over now!”
And he drew her closer to him, and fell asleep.
CHAPTER XXXI.
Next morning, when rest had restored him to a wider interest and
curiosity, George learnt the missing details of his adventure, and the
circumstances which had led to the journey of Rahas.
On finding that the pretext of her mother’s illness, upon which she
had been enticed to England, was a false one, Nouna, who now
mentioned the once loved name with averted eyes, but without any
other token of her suspicions, had felt guilty and uneasy about her
husband; and as she did not hear from him she slipped away one
night to find the house of Miss Glass, of whose kindness to herself
and fondness for George she retained a warm recollection. As she
felt ill and had no money, it was easy to guess how strong must have
been the feelings which prompted her to leave her mother’s house.
“If I could not be with you, I wanted to be with some one who knew
you and was fond of you, and would help me to get back to you,
George,” she explained.
She had trusted to luck to find her way from Eaton Square to
Kensington, and had been too much frightened to ask for direction.
At last however, when she was so tired and despondent that she had
sat down on a doorstep and begun to cry, a policeman had spoken
to her, and on learning that she had no money, that she wanted to
get to Filborough Road, that she was not sure of the number, but that
she had friends there, he asked her whether she thought she could
find the house if she were in the street, and suggested that she
should take a cab, and ask her friends to pay for it. He had then
hailed a hansom and put her into it, she had found the house without
much difficulty, and Miss Glass had taken her in and nursed her
carefully through a long illness which followed her rash adventure.
At this point of her story poor Nouna broke down in tears,
reminded of a disappointment which had cut her to the heart. “And—
my baby—never came after all,” she whispered in a broken voice,
with her head hung down in pathetic shame; “and I thought it was a
punishment because I came away without asking you, and I thought
you were offended and would never forgive me, because when I
wrote to Paris to tell you I was sorry and ill, and begging you to
come, I got no answer. For I did not know you were in prison, Miss
Glass would not let me know. It was not until weeks later, when—my
mother found out where I was, and told me she had seen you, that I
knew, and that I said I must come to you. So they let me go, with
Sundran, to Paris; and first they said you were at Poissy, and I went
there and asked to see you, and there they said perhaps you were at
Toulon. So we went to Toulon, and I wrote to the governor, and he
said I could see you in two months. I felt I could not live all that time,
and I was wondering what I could do to see you, when the great
storm came and damaged the harbour, and they said some of the
convicts would repair it. And my heart seemed to give a great bound,
for I felt that my wish had come true like that. So I crept down to the
harbour and slipped quietly along to the place where the stones were
washed away, and waited until I saw you. When the second day you
spoke to the warder-man and told him to send me away, I did not
mind, for I knew by your face you were not angry; so next morning I
wrote a message to you on the stone where you were working, and
Sundran brought me back to England, for I was getting ill again, and
she was afraid I should die there. And Miss Glass said I must go to
the south where it was warm, and she sent me to Plymouth to her
parents, and they are very kind and good to me.”
“And did you let that wretch Rahas come and visit you?” asked
George in a puzzled voice.
“I will tell you. I got a letter from him a few days ago, saying he
was going to France, and if I pleased, he could take a letter from me
to you, and let me see you, if I was anxious, as he used to let me
see—my mother. I had only to say yes, and he would come down to
Plymouth. I hated him for deceiving me and bringing me to England,
but he declared in his letter that was my mother’s doing. And I was
so hungry for some news of you that I wrote Yes, he might come.
Then I could not keep still for impatience: he telegraphed to me to
meet the train he came by, and I went to the station, and when I
found he hadn’t come by it, I described him to the guard, and he said
a dark gentleman like that had left the train two stations before.
There’s a big boy at the house where I’m staying who does whatever

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