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BIOSENSORS NANOTECHNOLOGY The second edition of Biosensors Nanotechnology comprises 20 chapters and discusses a wide range of applications exploited by biosensors based on nanoparticles including new domains of bionics, power production and computing. The biosensor industry began as a small, niche activity in the 1980s and has since developed into a large, global industry. Nanomaterials have substantially improved not only non-pharmaceutical and healthcare uses, but also telecommunications, paper, and textile manufacturing. Biological sensing assists in the understanding of living systems and is used in a variety of sectors, including medicine, drug discovery, process control, environmental monitoring, food safety, military and personal protection. It allows for new opportunities in bionics, power generation and computing, all of which will benefit from a greater understanding of the bio-electronic relationship, as advances in communications and computational modeling enable us to reconsider how healthcare is offered and R&D and manufacturing are enhanced. In this fast-evolving discipline, the combination of nanoscale materials with biosensor technology has gained a lot of traction. Nanostructures have been used to increase the adherence of biosensor materials to electrode surfaces, print nano barcodes on biomaterials, increase the pace of bio-responses, and amplify the electric signal. Some of the topics discussed in the book include: Bioreceptors for Cells; Bioreceptors for Enzymatic Interactions; Dendrimer-Based Nanomaterials for Biosensors; Biosensors in 2D Photonic Crystals; Bioreceptors for Affinity Binding in Theranostic Development; Biosensors for Glucose Monitoring; Metal-Free Quantum Dots-Based Nanomaterials for Biosensors; Bioreceptors for Microbial Biosensors; Plasmonic Nanomaterials in Sensors; Magnetic Biosensors; Biosensors for Salivary Biomarker Detection of Cancer and Neurodegenerative Diseases; Design and Development of Fluorescent Chemosensors for the Recognition of Biological Amines and Their Cell Imaging Studies; Application of Optical Nanoprobes for Supramolecular Biosensing; In Vivo Applications for Nanomaterials in Biosensors; Biosensor and Nanotechnology for Diagnosis of Breast Cancer; Bioreceptors for Antigen-Antibody Interactions; Biosensors for Paint and Pigment Analysis; Bioreceptors for Tissue; Biosensors for Pesticide Detection; and Advances in Biosensor Applications for Agroproducts Safety. Audience The book is written for a large and broad readership including researchers, industry engineers, and university graduate students from diverse backgrounds such as chemistry, materials science, physics, pharmacy, medical science, biomedical engineering, electronics engineering, and nanotechnology.

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Table of Contents

Cover

Table of Contents

Series Page

Title Page

Copyright Page

Preface

1 Bioreceptors for Cells

1.1 Introduction

1.2 Classification of the Cell as a Bioreceptor

1.3 Types of Nanomaterials Used in Cell Biosensor

1.4 Classification of Biosensors Based on Transducers

1.5 Application of Biosensors of Cells

1.6 Analytical Method for Biosensors of Cells

1.7 Recovery Time

1.8 Conclusion

References

2 Bioreceptors for Enzymatic Interactions

2.1 Introduction

2.2 History of Biosensors

2.3 Biosensors

2.4 Classification of Biosensors

2.5 Types of Bioreceptors

2.6 Transducers for Enzymatic Interactions

2.7 Enzymes and Enzymatic Interactions in Biosensor

2.8 Applications of Enzyme Biosensor

2.9 Conclusion and Future Expectations

References

3 Dendrimer-Based Nanomaterials for Biosensors

Abbreviations

3.1 Introduction

3.2 Biosensors

3.3 Dendrimers in Drug Delivery System

3.4 Dendrimers as Sensors

3.5 Conclusion

References

4 Biosensors in 2D Photonic Crystals

4.1 Introduction

4.2 Biosensors

4.3 The Overall Inference

4.4 Conclusion

References

5 Bioreceptors for Affinity Binding in Theranostic Development

5.1 Introduction

5.2 Affinity-Binding Receptors

5.3 Affinity-Binding Bioreceptors in Theranostic Applications

5.4 Conclusion

References

6 Biosensors for Glucose Monitoring

Abbreviations

6.1 Introduction

6.2 Development of Enzyme-Based Glucose Biosensors

6.3 Fabrication of Enzymatic Glucose Biosensors

6.4 Recent Trends for Development of Glucose Biosensors

6.5 Conclusion

Acknowledgment

References

7 Metal-Free Quantum Dots-Based Nanomaterials for Biosensors

7.1 Introduction

7.2 Metal-Free Quantum Dots as Biosensors

7.3 Conclusions

References

8 Bioreceptors for Microbial Biosensors

8.1 Introduction

8.2 Progression of Biosensor Technology

8.3 Biosensors Types

8.4 Why is a Biosensor Required?

8.5 Optical Microbial Biosensors

8.6 Mechanical Microbial Biosensor

8.7 Electrochemical Biosensor

8.8 Impedimetric Microbial Biosensor

8.9 Application of Bs in Various Fields

8.10 Recent Trends, Future Challenges, and Constrains of Biosensor Technology

8.11 Conclusion

References

9 Plasmonic Nanomaterials in Sensors

9.1 Introduction

9.2 Fundamentals of Plasmonics

9.3 Optical Properties of Plasmonic Nanomaterials

9.4 Fiber Optic and PCF-Based Plasmonic Sensors

9.5 Effects of Plasmonic Nanomaterials in PCF-Based SPR Sensors

9.6 Current Challenges and Future Directions

9.7 Conclusion

Acknowledgment

References

10 Magnetic Biosensors

10.1 Introduction

10.2 History

10.3 Structural Design

10.4 Numerical Analysis

10.5 Outcome Analysis

10.6 Conclusion

Acknowledgment

References

11 Biosensors for Salivary Biomarker Detection of Cancer and Neurodegenerative Diseases

11.1 Introduction

11.2 Biosensors for Neurodegenerative Diseases

11.3 Biosensor for Cancer

11.4 Conclusion

References

12 Design and Development of Fluorescent Chemosensors for the Recognition of Biological Amines and Their Cell Imaging Studies

12.1 Introduction

12.2 Chemosensors

12.3 Importance of Biogenic Amines

12.4 Conclusion

References

13 Application of Optical Nanoprobes for Supramolecular Biosensing: Recent Trends and Future Perspectives

13.1 Introduction

13.2 Optical Nanoprobes for Biosensing Applications

13.3 Conclusions and Future Perspectives

Acknowledgment

References

14

In Vivo

Applications for Nanomaterials in Biosensors

14.1 Introduction

14.2 Types of NM-Based Biosensors

14.3 Conclusion and Perspectives

References

15 Biosensor and Nanotechnology for Diagnosis of Breast Cancer

15.1 Introduction

15.2 Characteristics of Biosensors

15.3 Cancer Therapy with Nanomaterials

15.4 Diagnosis of Breast Cancer

15.5 Conclusion

References

16 Bioreceptors for Antigen–Antibody Interactions

16.1 Introduction

16.2 Antibodies: A Brief Overview

16.3 Antigen–Antibody Reactions

16.4 Antibody-Based Biosensors (Immunosensors)

16.5 Modified Antibodies as Bioreceptors: A Novel Approach

16.6 Conclusion

References

17 Biosensors for Paint and Pigment Analysis

Abbreviations

17.1 Paint and Pigments

17.2 Characteristics of Pigments for Paints

17.3 Analysis of Paints and Pigments

17.4 Biosensors and Their Background

17.5 Components, Principle and Working of Biosensors

17.6 Applications of Biosensors

17.7 Conclusion

References

18 Bioreceptors for Tissue

Abbreviations

18.1 Introduction

18.2 History

18.3 Tissue-Based Biosensors

18.4 Classification

18.5 Applications of Tissue-Based Biosensors

18.6 Generalized Areas Encompassing Biosensors

18.7 Conclusion

References

19 Biosensors for Pesticide Detection

Abbreviations

19.1 Introduction

19.2 Biosensors for Pesticide Detection

19.3 Electrochemical Immunosensors for Pesticide Detection

19.4 Applications of Nanomaterials for the Development of Pesticide Immunosensors

19.5 Conclusion

Acknowledgment

References

20 Advances in Biosensor Applications for Agroproducts Safety

20.1 Introduction

20.2 Biosensors for Safety of Plant Products

20.3 Biosensors for Safety of Animal Products

20.4 Biosensors for Safety of Microbes Used in Food Processing and Storage

20.5 Prospects and Conclusions

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Classification of transducer and its application.

Chapter 2

Table 2.1 Biosensing device based on transducer and their commercially avail...

Table 2.2 Analytes and various biosensor used fo their detection.

Table 2.3 Application of enzyme biosensors in various enzymatic interactions...

Chapter 3

Table 3.1 Techniques in surface modification of dendrimers.

Table 3.2 Drug properties improvised by dendrimers.

Table 3.3 Outlook shows the characteristics of dendrimers.

Table 3.4 Nanomaterials in biosensors.

Chapter 4

Table 4.1 Waveguide and cavity coupled waveguide-based structure.

Chapter 5

Table 5.1 Summary of theranostic applications of bioreceptors.

Chapter 6

Table 6.1 Generated glucose biosensors. Reprinted from Ref. [5] (copyright 2...

Table 6.2 Enzyme-based colorimetric glucose biosensors.

Table 6.3 Enzyme-based electrochemical glucose biosensors.

Chapter 7

Table 7.1 CQDs based metal-free materials as biosensors.

Table 7.2 GQD-based metal-free materials as biosensors.

Table 7.3 g-C

3

N

4

QD-based metal-free materials as biosensors.

Chapter 8

Table 8.1 A summarize of various microbial biosensor for detection of whole ...

Table 8.2 A summarize of various microbial biosensor described in the litera...

Chapter 9

Table 9.1 A comparison of various plasmonic materials and their sensing perf...

Chapter 10

Table 10.1 Different numerical parameters for the investigations of the sens...

Table 10.2 Overall performance analysis.

Chapter 11

Table 11.1 Biosensors for salivary biomarkers of neurodegenerative disorders...

Table 11.2 Biosensors for salivary biomarkers of cancer.

Chapter 12

Table 12.1 Comparison of different transduction methods used for the detecti...

Table 12.2 Assessment of various novel fluorescent probes for the hydrazine ...

Chapter 13

Table 13.1 Summary of the performance of zero-dimensional optical nano-biose...

Table 13.2 Summary of the performance of one-dimensional optical nano-biosen...

Table 13.3 Summary of the performance of two-dimensional optical nano-biosen...

Table 13.4 Summary of the performance of three-dimensional optical nano-bios...

Chapter 14

Table 14.1 Several nanomaterials used in biomaterials.

Chapter 15

Table 15.1 Roadmap of biosensors.

Table 15.2 NP-based drugs are used to treat different stages of breast cance...

Table 15.3 Types of organic NPs for cancer therapy [42].

Chapter 16

Table 16.1 Pros and cons of the three antibody types [4].

Table 16.2 Antibody biomarkers for detection of proteins.

Table 16.3 Antibody biomarkers for detection of metabolites [2].

Table 16.4 Antibody biomarkers for detection of pathogens.

Chapter 17

Table 17.1 Major breakthrough in pigment development [7, 8]

Table 17.2 Biosensors based on pigments with their applications.

Table 17.3 Applications of biosensors/sensors for different dyes and pigment...

Table 17.4 Applications of biosensors for estimation of organic and inorgani...

Chapter 18

Table 18.1 Plant and animal tissues with respect to their enzymes and substr...

Table 18.2 Types of biosensor and its application.

Chapter 19

Table 19.1 Electrochemical pesticide biosensors.

Chapter 20

Table 20.1 Screening technique for

salmonella

in poultry.

List of Illustrations

Chapter 1

Figure 1.1 Schematic classification of the biosensor of the cell.

Figure 1.2 Pictorial view of detection mechanism of cell biosensors through ...

Chapter 2

Figure 2.1 Progression of inventions in biosensors from first innovation to ...

Figure 2.2 Schematic representation of working of biosensor which indicates ...

Figure 2.3 Flowchart of classification of biosensors based on receptor, tran...

Figure 2.4 Types of enzyme immobilization techniques used in adaptation of r...

Chapter 3

Figure 3.1 Outlook of dendrimers structure [1].

Figure 3.2 Types of dendrimers, (a) polyester unit, (b) polyacetal unit, (c)...

Figure 3.3 Parts of dendrimer [1].

Figure 3.4 Dendrimers assemblies on the surface of electrode: (a) “monolayer...

Chapter 4

Figure 4.1 Block diagram of optical biosensor.

Figure 4.2 (a) Schematic diagram of sensor 1. (b) Schematic diagram of senso...

Figure 4.3 Design of two hexagonal biosensor.

Figure 4.4 L and inverted L waveguide biosensor.

Figure 4.5 (a) 3D structure of sensing element. (b) Sensor with inner ring h...

Figure 4.6 Infiltered photonic crystal biosensor.

Figure 4.7 Rhombic resonator for glucose concentration.

Figure 4.8 Elliptical resonator as biosensor.

Figure 4.9 Elliptical biosensor with gold and silicon nitride rods.

Figure 4.10 Ring resonator biosensor with GaAs rods.

Chapter 5

Figure 5.1 Drug delivery mechanism of antibodies [36], reproduced with permi...

Figure 5.2 Aptamer-Gold (Ap-Au) nanoparticle used to detect cancer cells [45...

Chapter 6

Figure 6.1 Schematic of the structure of an enzymatic glucose biosensor. Thi...

Figure 6.2 (a) Illustration of the working principle of a colorimetric gluco...

Figure 6.3 (a) First-generation enzymatic electrochemical glucose biosensor....

Figure 6.4 (a) A typical structure of an enzymatic electrochemical glucose b...

Figure 6.5 Working principle of a label-free enzyme-based colorimetric biose...

Figure 6.6 Working principle of an enzyme-based colorimetric GB combining GO...

Figure 6.7 Illustration of various strategies for GOx immobilization onto el...

Figure 6.8 (a) XRD pattern, (b) VSM plots, (c) FE-SEM and (d) TEM of FN-CNs,...

Figure 6.9 (a) Working principle of an enzymatic colorimetric glucose biosen...

Figure 6.10 (a) A structure layout of colorimetric-based PAD for glucose sen...

Figure 6.11 (a) Illustration of an enzymatic colorimetric glucose PAD using ...

Figure 6.12 (a) Photograph and schematics of the structure of a sweat-based ...

Chapter 7

Figure 7.1 Preparation of CQDs and B-CQDs [20]. Reprinted by permission from...

Figure 7.2 Fabrication of CDs-pDNA-/Fe

3

O

4

@PDA for sensing microRNA-167 [22]....

Figure 7.3 Interaction between CQDs and Co

2+

ions of Vitamin B12 [26]. Repri...

Figure 7.4 Photoelectrochemical detection of chlorpyrifos on NCQD/TiO

2

/ITO e...

Figure 7.5 Fabrication of (N-GQDs)/g-C

3

N

4

biosensor [42]. Reprinted by permi...

Figure 7.6 (a) PL spectra of g-CNQDs and g-CNQDs /PBA and (b) change in PL i...

Chapter 8

Fig. 8.1 Schematic representation of biosensor.

Fig. 8.2 Application of microbial biosensor in various field.

Chapter 9

Figure 9.1 Applications of plasmonic nanomaterials in sensors.

Figure 9.2 Noble plasmonic materials.

Figure 9.3 (a) Copper-based plasmonic biosensor, a(i) Schematic illustration...

Chapter 10

Figure 10.1 Applications fields of magnetic nanoparticles.

Figure 10.2 History of development of the magnetic sensor.

Figure 10.3 Simulated structures for a magnetic biosensor, including ((a) do...

Figure 10.4 Refractive index differences or birefringence value for differen...

Figure 10.5 The length of the coupling varies depending on the wavelength an...

Figure 10.6 Variations in Oe values and wavelength affect the PS [28, 29].

Figure 10.7 Variations in Oe values affect the TPS [27–29].

Figure 10.8 Sensitivity response for different Oe values [27–29].

Figure 10.9 Confinement loss spectrum for using different magnetic fluid [26...

Figure 10.10 Transmission spectrum for ring core fiber for different mode di...

Chapter 11

Figure 11.1 Main classification of electrochemical biosensors.

Figure 11.2 Main types of neurodegenerative diseases.

Figure 11.3 Biomarkers for AD.

Figure 11.4 Biomarkers for PD.

Figure 11.5 Biomarkers for HD.

Figure 11.6 Biomarkers for ALS.

Figure 11.7 Biomarkers of MS.

Figure 11.8 Four major cancer types that are fatal.

Figure 11.9 Salivary biomarkers for lung cancer [145–155].

Chapter 12

Figure 12.1 Schematic representation for the design of chemosensors. (a) The...

Figure 12.2 Structures of several important biogenic amines [10].

Figure 12.3 Structures of sensors 1-2 for histamine detection.

Figure 12.4 Histamine detection by a nickel bound calcein derivative 3.

Figure 12.5 Detection of tryptamine by sensors

4-6

.

Figure 12.6 (a) Fluorimetric photographs of 5 alone, 5 with various biogenic...

Figure 12.7 Spermine recognition by the different type of compounds (7–9).

Figure 12.8 Two distinct variants (

10-11

) for the identification of tyramine...

Figure 12.9 Structures for the hydrazine recognition by the diverse synthesi...

Figure 12.10 Polyamines detection by the modulation of two discriminate sens...

Figure 12.11 Compounds (21-24) for functioning as fluorescent chemosensors f...

Figure 12.12 The other set of various novel probes (25-27) for the aliphatic...

Figure 12.13 Structural representation three different sensors (29-30) for t...

Figure 12.14 Structure of synthesized neurosensor 31 for the detection of se...

Figure 12.15 Compounds (

32, 33

) developed for the specific sensing of dispar...

Chapter 13

Figure 13.1 Application of 0-D, 1-D, 2-D and 3-D nanomaterials for the targe...

Figure 13.2 (a) The schematic representation of dCDs synthesis towards fluor...

Figure 13.3 (a) Schematic description of DA sensing mechanism by N-GQDs, Ada...

Figure 13.4 (a) Schematic illustration of dQDs-FLISA procedure (b) The varia...

Figure 13.5 (a) Stages of biomolecule attachment on AuNPs surface. (i) prist...

Figure 13.6 (a) Proposed sensing mechanism of dopamine by IL capped AgNPs, (...

Figure 13.7 (a) Schematic representation of glucose sensing by mesoporous Mn...

Figure 13.8 (a) Schematic representation of ALP detection by polymer dots, A...

Figure 13.9 Schematic diagram of fabricating optical core-shell microfibers....

Figure 13.10 (a) Schematic diagram of H

2

S response of MSiNWs, (b) Fluorescen...

Figure 13.11 (a) Schematic demonstration of citrate ion (C

6

H

5

O

7

3-

) detection...

Figure 13.12 (a) Sensing mechanism of γ-Al

2

O

3

–GO/DNA/SF nanobiosensor, Adapt...

Figure 13.13 (a) Schematic depiction of MnO

2

NS-based ratiometric fluorogeni...

Figure 13.14 (a) Synthesis of Hybrid Nanoflowers (HNFs) with the addition of...

Chapter 14

Figure 14.1 Nanotechnology and NMs revolutionizing progress in agriculture, ...

Figure 14.2 Representation of a typical biosensor, which includes a biorecep...

Figure 14.3 SERS sensor implantation on an extremely permeable free-standing...

Figure 14.4 Short- and long-term impacts of SiNPs on

C. elegans

longevity an...

Figure 14.5 (a) Conceptual representation of D-Au NPs-based in vivo treatmen...

Figure 14.6 GQD-NPs (photographed with 488 nm excitation), blood vessels (ph...

Figure 14.7 (a) Schematic representation of the minimally intrusive l-Dopa s...

Chapter 15

Figure 15.1 A schematic design of a standard biosensor shows the transducer,...

Figure 15.2 Biosensor evolution timeline.

Figure 15.3 Nanotechnology aids in the identification and diagnosis of cance...

Figure 15.4 (a) Biosensors made of various nanomaterials. (b) Various NP syn...

Figure 15.5 Breast cancer detection and therapeutics based on nanotechnology...

Figure 15.6 Biosensors based on nanomaterials (nanobiosensors) [89].

Figure 15.7 Breast cancer detection with biosensors and nanobiosensors.

Figure 15.8 Biomedical technology makes use of nanobiosensors [90].

Figure 15.9 (a) clinical examination, (b) mammography, (c) ultrasonography, ...

Figure 15.10 Skin patchable sensor.

Chapter 16

Figure 16.1 A general structure of an antibody.

Figure 16.2 A flowchart depicting the types of antibodies.

Figure 16.3 The steps of production of polyclonal antibodies.

Figure 16.4 The steps of production of monoclonal antibodies.

Figure 16.5 The steps of production of recombinant antibodies.

Figure 16.6 Biosensing technologies used to determine Ig E-based allergy bio...

Chapter 17

Figure 17.1 Flowchart for classification of pigments/dyes.

Figure 17.2 Essential characteristics of pigments used in paints.

Figure 17.3 Diagram representing working principle of biosensors.

Figure 17.4 Applications of biosensors in various fields.

Chapter 18

Figure 18.1 Basic components of a biosensor including an analyte, biorecogni...

Figure 18.2 A schematic representation of the classification of biosensor fo...

Figure 18.3 A flowchart showing an outlook of applications of tissue based b...

Chapter 19

Figure 19.1 Illustration of pesticide biosensor construction. This figure is...

Figure 19.2 Classification of physical transducers. This figure is redrawn....

Figure 19.3 (A) Illustration of an AChE-based selective inhibition enzymatic...

Figure 19.4 (A) Enzyme-based electrochemical biosensor for TCh detection (AT...

Figure 19.5 (A) Working principle of bi-enzymatic biosensor for organophosph...

Figure 19.6 Electrochemical impedance spectroscopy (EIS) aptasensor for acet...

Figure 19.7 Schematic illustration of EIS aptasensors for acetamiprid and at...

Figure 19.8 Schematic diagram of AgNP-based colorimetric aptasensors for pes...

Figure 19.9 Illustration of working principle of nanoparticle-based colorime...

Figure 19.10 IgG antibody structure. This figure is redrawn.

Figure 19.11 Electrochemical immunosensor for 2,4-DB detection. This figure ...

Figure 19.12 Immunosensor for clenbuterol (CLB) detection. This figure is ta...

Figure 19.13 Immunosensors based on indirect detection mode: (a, b) traditio...

Figure 19.14 Electrochemical immunosensor based on label-free but indirect d...

Figure 19.15 Electrochemical biosensor for diuron detection based on Prussia...

Figure 19.16 Scheme of an electrochemical displacement immunoassay for couma...

Figure 19.17 EIS-based immunosenor for ATZ detection using nanoporous alumin...

Figure 19.18 (a) A coupled reaction of 5-hydroxy-1,4-naphthoquinone with hyd...

Figure 19.19 Working principle of a label-free EIS immunosensor for ATZ dete...

Figure 19.20 (A) A chemical synthesis of AgNPs/GO and AgNPs/GO/Nf for modifi...

Figure 19.21 Process for the fabrication of an ATZ electrochemical immunosen...

Chapter 20

Figure 20.1 Electrochemical BoS for detection microbial toxins in cereal foo...

Figure 20.2 Role of the BoS in preventing quality decline of fruit juices [3...

Figure 20.3 Typical BoS activity for feed safety detection [41].

Figure 20.4 Application of BoS for nisin detection in milk [50].

Figure 20.5 An immune-magnetic separation technique combined with an active ...

Guide

Cover Page

Series Page

Title Page

Copyright Page

Preface

Table of Contents

Begin Reading

Index

Wiley End User License Agreement

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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106

Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])

Biosensors Nanotechnology2nd Edition

Edited by

Inamuddin

Department of Applied Chemistry, Aligarh Muslim University, India

and

Tariq Altalhi

Department of Chemistry, College of Science, Taif University, Saudi Arabia

This edition first published 2023 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA© 2023 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.

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Library of Congress Cataloging-in-Publication Data

ISBN 978-1-394-16624-4

Cover images: Pixabay.ComCover design by Russell Richardson

Preface

The biosensor industry began as a small, niche activity in the 1980s and has since developed into a large, global industry. Nanomaterials have substantially improved not only non-pharmaceutical and healthcare uses, but also telecommunications, paper, and textile manufacture. Biological sensing aids in the understanding of living systems and may be used in a variety of sectors, including medicine, drug discovery, process control, environmental monitoring, food safety, military, and personal protection. It brings up new opportunities in bionics, power generation, and computing, all of which will benefit from a greater understanding of the bio-electronic relationship, as advances in communications and computational modeling are forcing us to reconsider how we offer healthcare and perform R&D and manufacturing to the modern world.

As a result of the customization of everything from health to environmental control, new payment structures and commercial models will arise. Wearable, mobile, and integrated sensors are being used in an increasing variety of products, but the majority of these devices still rely on physical sensors to measure elements like temperature and pressure. There is a conspicuous dearth of sensors that are both robust and convenient in the field of body chemistry sensors. This book examines emerging technologies that are accelerating scientific study and laying the foundation for new goods meant to extend and improve the quality of our lives. In this newly evolving discipline, the combination of nanoscale materials with biosensor technology is gaining a lot of traction. Nanostructures have been used to increase the adherence of biosensor materials to electrode surfaces, print nano barcodes on biomaterials, increase the pace of bio-responses, and amplify the electric signal. Finally, nanomaterial-based biosensors may be employed in a wide range of medical diagnostics and environmental monitoring applications due to their better response speed, greater sensitivity, simple design, specificity, and cost-effectiveness.

The book covers the major materials employed in the development of biosensors such as nanoparticles, nanowires, nanotubes, nanoribbons, nanorods, nanosheets, and many more nanostructures.

Chapter 1 discusses how the innovative techniques used in biosensors evolved from cell engineering and 3D cell immobilization. The various parts of biosensors based on cell detection using the cell’s bioreceptors are discussed in detail along with their working mechanism and applications.

Chapter 2 discusses the bioreceptors for enzymatic interactions as part of an enzyme-based biosensor to detect the analyte from a sample with applications. Materials used for the construction of various types of biosensors and types of bioreceptors, immobilization of enzymes for biosensors, and types of transducers for enzymatic interactions are also described.

Chapter 3 discusses the history, structure, synthesis, types, physical, and chemical properties including the merits and demerits of dendrimers in detail. This chapter focuses on dendrimers as drug delivery via electrochemical, enzymatic, optic, QCM, and glucose-based biosensors.

Chapter 4 details the importance and need for various 2D Photonic Crystal biosensors. The chapter discusses, in detail, how disease identification is done by measuring the effective change in the refraction of different analytes, and as well as various Photonic Crystal structures. It also focuses on the scope and future development of biosensors using 2D structures.

Chapter 5 explains that the applications of bioreceptors are numerous, ranging from bench-top analysis to point-of-care diagnosis and treatment. Hence, this chapter is an overview of common bioreceptors, especially affinity-binding receptors that are crucial in theranostic applications.

Chapter 6 details the brief history, basic working principles, and the present developments in glucose biosensors. The chapter focuses on fabrication methods and recent trends in the application of nanomaterials and nano/microfabrication for the development of paper analytical devices or wearable glucose biosensors.

Chapter 7 is focused on the recent progress in the preparation of metal-free quantum-sized sensors. The biosensing and detection applications of carbonaceous quantum dots such as carbon, graphene, and carbon nitride quantum dots are investigated. Optical and electrochemical techniques are discussed with a consideration for the limit of detection values.

Chapter 8 details the latest research progress on bioreceptors for microbial biosensors. In addition, it summarizes the types and applications of microbial biosensors: the recent trend and the future challenges of microbial biosensor technology.

Chapter 9 explains the use of several noble plasmonic materials including gold, silver, copper, niobium, and aluminum, and their widespread applications in optical sensing and sensors. Also, the advantages, disadvantages, and prospects of some highly used plasmonic nanomaterials in sensors are discussed in this chapter.

Chapter 10 explains the differences between various magnetic sensors and their accompanying sensitivity responses and consequences. This chapter discusses how magnetic sensors use magnetic fluids for studying the impact on a range of particles and various sensor architectures for tracking biological interactions with distinct magnetic strength change.

Chapter 11 deals in detail with the various salivary biomarkers and the biosensors associated with several neurological disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, multiple sclerosis, autism spectrum disorders, and neuropsychiatric disorders, and various cancers affecting breasts, lungs, pancreas, and the gastrointestinal system.

Chapter 12 deals with the different molecules for biological amine detection by fluorescent chemosensors and its specific emphasis on the use of bioimaging applications. In addition, the sustained improvements in fluorescent biosensors are anticipated to result in universal biosensors for essential biological amines, which can be detected in real-time analysis.

Chapter 13 provides concise information about chromo-fluorogenic biosensing applications of diverse nanomaterials including zero, one, two, and, three-dimensional nanomaterials. Biosensing from complicated bio-matrices along with intracellular imaging is also discussed. Finally, loopholes of present research and future research directions are also outlined to stay current with medical diagnosis.

Chapter 14 explores present and prospective breakthroughs in nanotechnology-based biosensors for real-time assessment of several analytes and the toxicity mechanisms in living creatures, using primary datasets from 2018 onwards. Innovative biosensing technologies centered on unique sensing components and transduction concepts receive special attention. The chapter also discusses the opportunities and future considerations for the utilization of NMs-based biosensors for enhanced environmental and food-sensing devices.

Chapter 15 deals with the introduction and roadmap of biosensors, followed by the use of nanotechnology in cancer therapy. Additionally, it explores nanomaterial infused with a biosensor, the fabrication of nano biosensor, and the diagnosis of breast cancer, including point-of-care and wearable analysis.

Chapter 16 provides a brief overview of antibody-based biosensors, also called immunosensors. The chapter includes a discussion on antigen-antibody interactions and the application of immunosensors in various areas of the health and food industries. Lastly, some new approaches to antibody modifications that offer several advantages over classical antigen-antibody receptors are also discussed.

Chapter 17 describes the use of biosensors for various paints and pigment analysis. It discusses the biosensor’s components, history, and working principle in regard to paint and pigments. For future benefit, the chapter describes the characteristics of paints and pigments, with analytical methods, and various applications of paints and pigments-based biosensors.

Chapter 18 discusses biological devices that are incorporated into various animal and plant tissues. The applicability in varied physiology along with its distinguished classification based on different principles is covered also. Furthermore, the chapter enumerates the increasing exigencies for these devices in a broad range of areas including various medical ailments.

Chapter 19 details various methods for pesticide detection with simple, highly selective and sensitive, fast response, cost-effective and portably sized biosensors. The chapter also discusses recent results from the use of nanomaterials in the fabrication of pesticide biosensors in food and environmental applications.

Chapter 20 discusses the applications of biosensors for monitoring the behavior of agro-products. Two categories of biosensors are highlighted, and their roles in detecting contaminants in dairy processing are discussed. The application of receptor-based biosensors was proposed for monitoring the survival rate of bacteria in milk processing.

The EditorsAugust 2023

1Bioreceptors for Cells

Vipul Prajapati1* and Salona Roy2

1 Department of Pharmaceutics, SSR College of Pharmacy (Permanently Affiliated to Savitribai Phule Pune University), Sayli-Silvassa Road, Sayli, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India

2 Department of Pharmacology and Toxicology, NIPER Hajipur, Export Promotions Industrial Park (EPIP), Industrial Area Hajipur, Dist. Vaishali, Bihar, India

Abstract

A biosensor is a tool that quantitatively determines the disturbance in the homeostatic equilibrium in a system in an extremely low concentration in the healthcare sector, such as diagnosis, treatment, and mitigation. Biosensors utilize specific biomarkers to aid in an accurate diagnosis based on its sensitivity, reproducibility, biocompatibility, and robustness, which has several advantages over conventional diagnosis, including onsite diagnosis in less time. This article covers various techniques involved in the pretreatment of the cell to modify certain bioreceptors, types of transducers, and their wide arena of application. Cells for biosensors are often labeled with certain enzymes or secondary substances producing an intensifying response of intrinsic signal transduction. The efficacy of a single mini device had attracted the attention of many researchers to aid in the early diagnosis of life-threatening diseases. Although enhancement in the performance of biosensor of cell has been going on, it has provided a gateway to next-generation approaches in the healthcare system.

Keywords: Cell, biosensor, diagnosis, treatment, bioreceptor

1.1 Introduction

Living cells are the biorecognition elements since they can detect any unknown stimuli or perception from their environment as a method of adapting, as well as surviving. Cell biosensors can detect analytes with utmost accuracy, high sensitivity, and specificity in a cost-effective, invasive or non-invasive way. They are appropriate bioreceptor elements because they provide versatility in sensing tactics and make production relatively straightforward and inexpensive when compared to pure enzymes, DNA, and antibodies-based detection techniques, such as ELISA, RIA, etc. [1].

Biosensors utilize a mixture of biological, chemical, and physical technologies to measure micro physiological signals in real-time and on-site detection. A biosensor system is made up of a few crucial elements like biological sample receptors, transducers, backing laminate, and display systems that use electrical, chemical, or photonic components. It is to detect the results and then turn the cascading event of recognition into a measurable signal strength, which can be grouped in conjugated and integrated biosensors [2].

A biosensor’s basic principle is to detect the bio-element at the molecular recognition level and convert it into a different sort of signal strength using a transducer [3]. Living cells, bioactive substrates, and transducers make up cell-based biosensors. The impact of biochemical or pharmacological compounds on cells might be measured by changes in cellular polarity or physiological characteristics like cell membrane permeability or ligand expression on biosensors after treatment [4]. Rapid analysis of small amounts of data as compared to conventional techniques, with the added benefit, may be used for the basis of clinical evaluation that integrated design platforms. The ability of sensor cells to detect specific analogs of targets while distinguishing them from structural counterparts that had no functional similarities within them provided the basis for accurate results [5].

Biosensors of cells have sparked attention as a potential alternative to traditional sensing methods due to several benefits, which include affordability and mobility with the major advantage of the absence of equipment and trained staff. Another pleasing characteristic of biosensors of cells is their versatility in terms of design and outputs, which made them capable of being adjusted to the unique feature whenever needed for desired outputs. They provide a diverse platform for analytical applications in various arenas, such as food, biomedical science, environmental, and society healthcare by merging disciplinary technologies and expertise. Environmental monitoring, bioproduction, biomedical applications in diagnostics, and health monitoring are all possible scopes for cell-based biosensors [6].

1.2 Classification of the Cell as a Bioreceptor

With the greater selectivity to target molecules, bio-elements, such as functional enzymes, serum antibodies, DNA, and other elements, have traditionally been used as bioreceptors in biosensing. Living cells, on the other hand, provide an intriguing alternative to these molecular bioreceptors due to their broad diversity of biomolecular processes [59]. Cell biosensors have been classified by many researchers based on biorecognition element and signal transduction but in this section, in another way they can be classified based on the structural system and extensive work done in the lab to convert a cell into a probe, i.e., cell pretreated in the lab or which utilizes the invasive method of detection and cell without pretreatment or utilizes non-invasive method as shown in Figure 1.1, which is sensitive enough to record and display on-the screen with the maximum level of accuracy.

Figure 1.1 Schematic classification of the biosensor of the cell.

1.2.1 On the Basis of Cell Origin

1.2.1.1 Mammalian Cell

The key transducers for signal creation in mammalian cell-based sensing systems are mammalian cells. When analytes excite living cells, the transducer converts changes in physiological characteristics or biological responses into a measurable and processable signal, fulfilling the detection and analysis goal [60].

Biosensors based on mammalian cells have been touted as potential instruments for pharmacology and toxicology, drug discovery, bioassay of drug substance, pathogen and toxin screening, environmental monitoring,, and biosafety research. The binding of cellular receptors to external substances triggers the cell–analyte interaction. The future of next level of generation biosensing techniques that use natural bio cellular receptors like GPCRs or the nicotinic in cholinergic receptor to measure the ligand-based secondary cellular response have been considered as shown in Figure 1.2 [61].

Hematopoietic and nervous system stem cells have been identified and grown in vitro. They develop into cell types, including neurons and myocardiocytes, which spontaneously contract in culture when induced to differentiate. Understanding neural network function from cells structured in vivo has been highly beneficial using brain tissue slices. Using isolated populations of cells as sensors ignores the analyte’s involvement in the in vivo cell metabolism developing coculture systems to expand the operational sensitivity of excitable cells to include metabolites would improve the current capabilities [62].

Figure 1.2 Pictorial view of detection mechanism of cell biosensors through GPCR receptor.

1.2.1.2 Microbial Cell

In the creation of biosensors, microbes are a good substitute for enzymes. They may be manufactured in vast quantities biotechnologically, and microbial cells contain multiple enzymes with the requisite cofactors or coenzymes, allowing them to detect a wide range of substrates. Furthermore, enzymes are very stable in their natural environment and do not require isolation [63].

In a variety of biological systems, biosensors of microbial detection are based on illumination from bacteria that are being used as a sensitive, fast, and non-invasive test. Bioluminescent bacteria may be found in a variety of habitats, from the sea to the land. Bioluminescent-like organism biosensors have also been created for the detection of organic, pesticide, and lead or mercury-like heavy metal pollution utilizing genetically engineered microorganisms (GEM). Cellular organelles can be thought of as multi-oriented biocatalysts that fall between complete cells and enzymes in terms of complexity [64]. In the manufacturing of biosensors, enzymes are the most extensively employed biological sensing element. Although pure enzymes have a high selectivity for their substrate, their use in biosensors may be restricted by the time and expense of enzyme purification, the necessity for numerous enzymes to make the measurable product, or the requirement for a coenzyme [65].

Viable cells and nonviable cells are the two types of cells found in microbes. The assessment of biological oxygen demand (BOD) or the consumption of other growth is two of the most common uses of living cells. Pollutants and hazardous substrates can also be detected by viable cells. Both virulent and dead microbial cells are utilized in the immobilization of microbial-based biosensors, although their immobilization needs varied. In case of utilization of an external light source, bacterial-based fluorescence occurs in an entire cell, and the fluorescence emission or radiating intensity is precisely proportional to the amount of analyte detection at very lower concentration [66].

Immobilized yeast was used to detect formaldehyde and assess the toxicity of cholanic acids, with changes in metabolism indicative of the analyte measured by O2 electrode readings or extracellular acidification rates. Organophosphate hydrolase is an enzyme that creates protons during the breakdown of organophosphate insecticides or nerve agents including sarin, soman, and VX. Analyte detection has been proposed using pH changes in the effluent from these immobilized cells [62].

1.2.2 On the Basis of Cell Treatment

1.2.2.1 Cell Pretreated in the Lab or Invasive Detection as Bioreceptor

The cell biosensors can be further classified on the basis of treatment of the cell or modified cell for construction of the biosensor. The methods for cultivating biological live cells on two-dimensional (2D) chip technologies are known as cell culture on-chip. Due to the advent of the scale of the grown environment within the micro-sized chip is tailored to the length of the cells, microchip approaches can give several benefits for cell culture systems.

1.2.2.1.1 Cell Immobilization Techniques

Cell culture of different cell types-based detection involving biosensing techniques use the stimulated response to the external stimuli mediated by a transducer through the modified signal. Immobilized enzymes can be utilized again after the completion of one process and they have higher stability in terms of catalytic activity than mobile enzymes. Although they have a lower catalytic rate when compared to mobile enzymes and require extensive treatment steps, immobilized enzymes are commonly used in medical and industrial plants because of benefits such as fast and efficient control by reusable enzymes i.e., ease of separation of the enzymes from the final product, maintaining purity of the product and high stability of the immobilized enzyme. There are mainly five methods of enzyme immobilization that can be classified as: adsorption, encapsulation, covalent bonding, entrapment as well as cross-linking, among all five, adsorption and covalent bonding method is mainly preferred. Adsorption, encapsulation, and entrapment are termed physical methods of immobilization whereas cross-linked covalent bonding is termed chemical methods or ways of immobilization [31]. Adsorption is one of the simplest techniques of immobilizations, it relies on the only weak force of attraction between enzyme and carrier such as London forces, electrostatic or ionic contacts, and hydrophobic or lipophilic interactions between them. As an extra reagent is not required, the adsorption approach is simple and affordable, moreover it is less damaging to enzyme function than other methods. On the other hand, because of their weak interaction, the enzyme immobilized by this approach are quickly deposited by changes in experimental setups like temperature, pH, or ionization potential.

Furthermore, contamination and signal interference may result from the non-targeted adsorption of various substrates onto a surface. Second, one of the most extensively utilized ways is covalent bonding, which creates stable complex compounds between enzymes and supports or carriers. The covalently immobilized enzymes have stronger binding than the adsorption and this method can provide more stable enzyme immobilization. Despite its advantages, the development of covalent bonds reduces the activity of the immobilized enzymes, and this approach necessitates a considerable amount of bioreagent to be used with it. Third, entrapment is not directly coupled to substrates or products; rather, it is entrapped or encased in polymers, which creates room for substrates and end-products to freely spread. Polymerization can take place in a combination of enzymes and monomeric units to entrap enzymes. Entrapment, like covalent bonding, is a physical interaction that offers the enzymes excellent stability and reduces leaching. Fourth, cross-linking provides strength to the bonded enzymes and ensures the leakage of enzymes during the utilization. It gives one of the very strong and robust connections between enzymes, the immobilization method via cross-linking enhances efficiency and stability. The use of cross-linking reagents like GTA (Glutaraldehyde), on the other hand, can result in a loss of activity due to severe modifications of the functional and non-functional enzymes caused by covalent bonding linkage. Fifth, encapsulation, which is more similar to that of the entrapment process, the only difference, lies in the arrangement of enzymes within the system. The encapsulation method involves the collection of enzymes in the semipermeable membrane and entrapment involves the arrangement of enzymes in the matrix forming structures. These biosensing devices are capable of reliably detecting water toxicity, assuring human safety and aquatic life welfare [32–34].

1.2.2.1.2 Microcontact Printing

The modification of surface technique that uses custom inks to modify surface chemical and biological signals as well as manufacture particular topographical characteristics is widely known as Micro-contact printing (MCP). In 1993, it had been proposed that the combination of MCP as a matter for regulating the concentration and area distribution of proteins will be adsorb onto to the designed self-assembled monolayers (SAMs). SAM is a part of the soft lithography method family, which is one of the most widely utilized surface modification techniques in biomedical applications. MCP has considerable benefits over other surface patterning methods in terms of cheap cost, high dependability, and adaptability. Two of MCP’s main duties in adjusting the surface are the creation of organized geometric or characteristic patterns and 2D surface designing. The similarity with nanoimprinted lithography lies in creating intricate patterns as in the case of MCP. MCP is a flexible surface modification technology that may manipulate surface chemical and biological signals as well as produce specific topographical features using specialized inks.

The primary distinction is that in nanoimprinted lithography, the stamp is made out of surface structured materials that have been created using processes like photolithography and another process known as the femtosecond laser ablation technique. The primary merit of MCP in comparison with the other surface modification methods lies in its good two-dimensional surface patterning capability, which allows varied functional groups or polysaccharides, proteins, and biological signals to be cast or transferred onto the surface of the substrate in precisely specified patterns. MCP has considerable benefits over other surface patterning methods in terms of cheap cost, high dependability and adaptability. Even though mechanical action regulated by a preset program ensures sample reproducibility and speed, it also allows for large-scale tailored manufacturing. This approach had been studied and implemented in a variety of sectors, and it has shown great promise in facilitating multidisciplinary study in science, engineering and medicine, with new applications being developed all the time. MCP’s operating settings may be gently tweaked and improved to generate excellent surface patterns on a range of substrates, despite of its basic premise [35].

1.2.2.1.3 Fast Ink-Jet Printing

Ink-jet printing is commonly used to accumulate a range of patterns on flexible and tangible substrates for conveniency, environment friendly, high process control, and low-cost electronic devices, among the various nanostructure deposition procedures on electrode surfaces. This method combines spatial resolution, printing speed, repeatability, inexpensive initial investment, and reduced waste into an attractive package. Inkjet printing also eliminates the need for dyes, masks, coloured chemical etchants using etching, and other patterning issues by printing the desired device pattern directly to the substrate. On a number of substrates, inkjet printing has been used to manufacture a range of electrical devices, sometimes in concert with other deposition or patterning processes [36].

Inkjet printing is an old practice that has lately been resurrected for the manufacturing of low-cost and simple electrical sensing and biosensing devices. This technology may be used to create flexible microsystems on ecologically friendly substrates like polymers and paper. Inkjet printing stands out among them because it blends an old-fashioned printing technology with cutting-edge nanoparticle-based inks to provide the printed device important qualities including conductivity, hydrophobicity or hydrophilicity and resistance or insulating properties. The technology was even utilized to use other bio-element such as enzyme, antibody and genetic material-based inks to functionalize the printed devices. This approach has been investigated in the biosensor sector for the past ten years, resulting in a vivid large number of papers as well as intriguing prospects and applications. Inkjet printing has several benefits over other printing processes, including the ability to print on both solid and flexible substrates, the lack of extra components other than inks, and the ability to reduce the time from concept to prototype to a few minutes and therefore it has been produced for electrochemical and optical biosensing by some companies [37].

1.2.2.1.4 Self-Assembled Monolayer

The two-dimensional molecular level structures that form or cast spontaneously on the surface of different kinds of substrates, hence known as Self assembled monolayer (SAMs). Self-assembly is the most versatile concept in nature as such around all biomolecules of larger size to smaller size, such as proteins, peptides, amino acids combine and self-assemble to produce functionally relevant structured and ordered structures. Proteins or short chain polypeptides have been used by nature to build a range of materials, including shells, pearls, and keratin. It may be used to create whole new molecular structures. SAMs are gaining popularity due to their applications in electrical devices such as biosensors, thin film transistors, micropatterning, etc. Molecules by molecules are assembled in self-assembly, thereby “bottom up” approach language is used. The notion of SAMs is gaining prominence in the field of modification of surface using biomaterials or biological compounds. SAM has a number of advantages over other physical surface modification techniques including UV irradiation and electron beam. Since the SAM surface modification enables for covalent bonding of molecules, one of the core advantages is their long shelf life or functional period. SAMs employing the aforementioned physical approaches, on the other hand it has shown low stability. In some cases, results in a loss of surface chemical activity as a result of irradiation. Furthermore, conventional approaches such as physical or chemical adsorption, London forces, and cross-linking of biomolecules had suffered from some stability issues, but the SAM approach has become widely used for biomolecule immobilization. There are two types of SAM which are small molecule SAM and polymer SAM and also there are two types of SAM production processes, substrate coupled and substrate decoupled, based on interactions between the substrate and the molecule of SAM. For instance, in the first stage, SAM headgroups chemisorb on certain areas of the surface to form an ordered monolayer which have been done experimentally in lab involves saturated thiols on a gold surface. In this case, the substrate’s crystalline structure is crucial, and single crystals such as gold are often used to create the ordered and linear assembly. In a substrate-decoupled process like the synthesis of alkyl siloxane on a substrate of silicon which is in hydrated form, there is indirect contact with the surface molecules, and the building of monolayer process is entirely controlled by intermolecular force of interactions [38–40].

1.2.2.1.5 Microfluidic Technology

Microfluidics are techniques for regulating small-scale fluids in devices and systems, and many microfluidic based devices have been actively and widely used in the replication and evaluation of specific and targeted biological processes in tiny devices with a limited quantity of material. Using microfluidics as an instrument to replace the existing conventional research equipment at a very minimal cost, cell counting, sorting and trapping have been reduced to a good extent. In various research, organizations have developed their specific microfluidic cell culture technique that had imitated like the exact organs of human beings in order to study targeted biological processes or evaluate the efficacy or toxic potential of drugs. Microfluidic based impedance virus biosensors have been intensively investigated because they rely on a simpler and faster method of identifying particular viruses than existing methods. One of the main advantages of microfluidic devices lies in the intrinsic capacity of the device to install many analytical modalities or elements; as a result, MFT biosensors have been created for applications ranging from utilization in an analytical instrument, in research to healthcare and associated industry. Some researchers developed a technique that can be used to test influenza of avian or bird virus with high degree of sensitivity using a portable impedance-based biosensor with twenty-five pairs of micro-electrodes were gathered and a microfluidic technology, as well as magnetic nano particles coated with antibodies [24].

1.2.2.2 Cell Without Pre-Treatment or Label-Free or Non-Invasive Detection

Live cells carefully perceive and respond to outside information. For quite some time, cell transmission was thought to be linear, with an ambient stimulus triggering a series of steps that culminated in a well-defined detection response. However, there is compelling evidence that are more complex when cellular reactions take place in response to external stimuli. The spatial and temporal targeting of proteins to suitable locations, which dictates the timing and strength of cell signals and responses, influences the specificity and effectiveness of various protein interactions. Cell signaling mediated by a cellular target like the G protein-coupled receptor (GPCR) is generally well-ordered and regulated, including a succession or series of spatial (space) and temporal(time) events, many of which result in alteration in localized mass density or redistribution of cell-based contents. When these changes or redistributions within the cell occur with the detecting volume, this process was followed by the optical sensors. This is because non-specific optical responses of cells recorded with a label-free biosensor are often overlooked. Optical biosensors can detect receptor signaling in real time and provide a kinetic optical signal when the ligand is administered. Since a receptor may interact with several signaling molecules and proteins scaffolding such as arrestins while simultaneously linking to multiple G protein subtype. Important cellular decisions like cytoskeletal remodeling, cell cycle checkpoints, and death need precise temporal or time specific control and relative spatial moreover space dimension distribution of active signal-transducers [28]. Due to its non-invasiveness at the micron scale, another use might be to track the evolution of a disorder or disease and find sensitive chemicals that would ordinarily be metabolized or inactivated in various biological samples utilized for clinical testing, such as serum, urine, or faeces [29]. A typical electrochemical sensor device for non-invasive epidermal consists of an adhesive single top layer membrane, a flexible or stretchy substrate positioned over the adhesive single membrane, and an anodic electrode assembly containing an iontophoretic electrode deployed over the flexible or stretchable substrate. Above the flexible or stretchy substrate, an iontophoretic electrode and a cathodic electrode assembly were kept close to the anodic electrode assembly. The device has an electrode interface assembly with several electrically conducting connections [30]. In most label-free biosensors, a transducer is employed to change a stimulus-induced biological interactive reaction into a readable and countable signal. Depending on the principle of the transducers, the label-free biosensors for whole cell sensing technique are classified as electric biosensors [29].

1.3 Types of Nanomaterials Used in Cell Biosensor

The size and dimensions of nanomaterials are used to classify them. Nanomaterials come in four different dimensions: zero, one, two, and three. The existence of three dimensions of materials in nanoscale of nano particles (NPs) of inert elements such as gold, palladium, platinum, silver, or quantum dots are nanomaterials having zero dimension. With a diameter of 1electron 50 nm, NPs can be spherical in shape. Zero-dimensional nanomaterials have been discovered in the form of cube and polygon forms. One dimension of 1D nanomaterials is in the region of 1electron 100 nm, whereas the other two dimensions might reach macroscale. One-dimensional (1D) nanomaterials include nanowires, nanofibers, nanorods, and nanotubes. 1D nanostructures may be made from inert metals, metal oxides, quantum dots, and other materials. The two dimensions are nanoscale whereas one dimension is macroscale in the 2D class of nanomaterials. Two-dimensional (2D) nanomaterials include nano-sheets, and nano-walls, nano-thin films, thin-film multilayers. 2D nanomaterials can have a surface area of several square micrometres while maintaining a thickness in the nanoscale range. There are no nanoscale dimensions in three-dimensional (3D) nanomaterials but all dimensions are macroscale in nature. Loaded materials are collection of 3D nanomaterials which is made up of individual blocks that can be as small as a nanometre or larger than that as well [58].

1.4 Classification of Biosensors Based on Transducers

1.4.1 Conjugated Biosensor

1.4.1.1 Electrochemical Biosensors

The biosensor which is a common sensing device that works by converting biological processes into electrical signals on the principle of electrochemical conversion. An electrode serves as stable base for biomolecule immobilization and electron flow which is considered to be a critical component. Various biosensing approaches for inexpensive and small analytical instruments for surface analysis have recently been developed [8]. Depending on type of electrical information is to be measured to get appropriate information, the electrical biosensors are subdivided into three main categories such as potentiometric, amperometric, and impedance sensors. Recent biosensor development has concentrated on critical aspects such as quick detection, detection limit, operation practicality, and low cost. Some electrochemical based pathogen detections have been performed by some researchers like Salmonella was identified which utilises a carbon electrode in screen printed fashion conjugated with immunomagnetic beads and an amperometric biosensor. A nanofiber based on light potentiometric sensor which can detect E. coli at very lower concentrations range under one hour had been developed. Some have reported an AuNP-based signal-off impedimetric immune-biosensor for detecting E. coli [9].

1.4.1.1.1 Amperometric Biosensors

Amperometric biosensing technologies have long been employed in medical settings. The sensing transducer in such sensors is made up of three electrodes termed as working, reference, and counter electrodes. Bioreceptors are immobilized on the working electrode whereas all electrodes are immersed in a specific range buffer solution. One electrode serves as working while other serves as the reference as well as counter electrodes in a two-electrode sensor. In most cases, the sensor is connected directly to a signal system that consist of a battery of specific voltage and a circuit working system. The circuit system controls the voltage of a battery to ensure that the sensor receives sufficient power.

Few researchers have worked on the amperometric biosensors where the sensing transducer’s two electrodes are linked to the battery’s cathode and anode. Lactate oxidation is catalyzed on the working electrode by immobilized lactate oxidase, which produces hydrogen peroxide (H2O2). H2O2