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The book offers a thorough exploration of revolutionary nano-biosensor technologies that enables rapid, accurate detection of infectious diseases, critical for effective disease management in today’s world.
Nano-Biosensor Technologies for Diagnosis of Infectious Diseases delves into the cutting-edge developments in nano-biosensor technology, a transformative innovation for the field of medical diagnostics. Nano-biosensors integrate nanomaterials like nanoparticles, nanowires, and nanotubes with biological recognition elements such as antibodies, nucleic acids, or enzymes to create highly sensitive and specific detection systems. These sensors exploit unique properties of nanomaterials to detect minute quantities of pathogens or biomarkers with remarkable accuracy, enabling early diagnosis and monitoring of infectious diseases. The integration of electrochemical, optical, and piezoelectric detection mechanisms further enhances the versatility and efficiency of these nano-biosensors, allowing for rapid, real-time analysis that is crucial for effective disease management.
In the context of infectious diseases, nano-biosensors become particularly significant, as they can facilitate point-of-care testing (POCT), offering rapid and portable diagnostic solutions. This capability is invaluable in resource-limited settings and during outbreaks where traditional laboratory infrastructure may be lacking. The COVID-19 pandemic underscores the importance of swift and accurate diagnostic tools, spurring accelerated innovation and commercialization efforts in this domain. Nano-biosensors are now being developed and deployed to detect a wide range of pathogens with high sensitivity, providing a powerful tool in the global fight against infectious diseases. Nano-Biosensor Technologies for Diagnosis of Infectious Diseases provides a comprehensive overview of these technological advancements, exploring their applications, challenges, and future directions in the diagnosis and management of infectious diseases.
Audience
Biomedical engineers, material chemists, researchers, students, policymakers, and healthcare professionals interested in integrating nanomaterials in infectious disease care
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Cover
Table of Contents
Serie Page
Title Page
Copyright Page
Preface
1 Biosensor Technology: Basic Principles, Fundamentals, and History
1.1 Introduction
References
2 Design and Synthesis of Novel Nanomaterials Emphasizing Infectious Diseases
2.1 Introduction
2.2 Antifungal Therapy
2.3 Cutting-Edge Advances in Tailoring the Size, Shape, and Functionality of Nanoparticles and Nanostructures
2.4 Gold Silver Nanoparticle to Combat Multi-Drug Resistant Pathogen
2.5 Mechanism of Gold Silver Nanoparticle to Combat Multi-Drug Resistant Pathogen
2.6 MXenes and Borophene Nanomaterials: Highly Efficient Sensor Activity and Energy Storage Properties
2.7 Immunomodulatory Nanosystems
2.8 Lateral Flow Assays (LFAs)
2.9 Metal-Organic Framework (MOF)
2.10 Microfluidic Devices: For Detecting Disease-Specific Proteins
2.11 Comprehensive Overview of Nanomaterials in the Context of Cutaneous Leishmaniasis
2.12 Graphene Oxide (GO): A Two-Dimensional (2D) Nanomaterial
Conclusion
Future Prospect
Acknowledgement
Authors’ Contributions
References
3 Role of Nanomaterials in the Development of Nanobiosensors for Infectious Diseases
3.1 Introduction
3.2 Designing Biosensor for SARS-CoV-2
3.3 Conclusions and Future Perspectives
References
4 Nanobiosensors: Versatile Tool for Diagnosis of Infectious Diseases
4.1 Introduction
4.2 Nanobiosensors as Promising Devices for the Diagnosis of Coronavirus Family Members
4.3 Nanobiosensors for Plant Analysis
4.4 Three-Way Junctions Skeleton of Biosensor
4.5 The SpACE-CCM: Biosensor for Detection of SARS-CoV-2 Spike-ACE2 Interaction
4.6 Wearable Biosensor Nano and Microsystems Have Emerged as Innovative Solutions for Medical Diagnostics
4.7 Biosensors are Analytical Devices
4.8 Conclusion
Acknowledgement
Authors’ Contributions
References
5 Trends in the Development of Immunosensors for the Diagnosis of Infectious Diseases
5.1 Introduction
5.2 Immunosensors
5.3 Optical Immunosensor
5.4 Nanomaterials Immunosensor
5.5 Paper-Based Immunosensors
5.6 Viral Infectious Diseases
5.7 Future Perspectives and Conclusion
Acknowledgements
References
6 Electrochemical Nanobiosensors Approaches for Rapid Diagnosis of Infectious Diseases
6.1 Introduction
6.2 Conventional Methods for the Determination of Infectious Pathogens
6.3 Building Blocks of Biosensor
6.4 Electrochemical-Based Biosensors
6.5 Impact of Nanomaterials on Biosensor Performance
6.6 Noble Metal Nanomaterials
6.7 Metal Oxide Nanomaterials
6.8 Carbon Nanomaterials
6.9 Polymer Nanomaterials
6.10 Bionanomaterials
6.11 Conclusions and Future Perspectives
Acknowledgement
References
7 Enzymatic Nanobiosensor Strategies to Contain the Spread of Infectious Diseases
7.1 Introduction
7.2 Components of Enzymatic Biosensor
7.3 Enzymatic Nanobiosensors for Pathogen Detection
7.4 Nanozymes
7.5 Future Aspects
References
8 Development of Optical Nanosensors for the Detection of Infectious Diseases
8.1 Introduction
8.2 Overview of Biosensor
8.3 Introduction to Optical Nanosensors
8.4 Remarks
References
9 Aptasensors: Selective and Powerful Tools for Infectious Diseases Diagnosis
9.1 Introduction
9.2 Aptamers as Selective and Powerful Tools for Diagnostics
9.3 Synthesis of Aptamers
9.4 Application of Aptasensors in PoC Diagnostics
9.5 Aptasensors Impact on Infectious Disease Diagnosis
9.6 Drawbacks and Potential Future Work
9.7 Conclusions
References
10 Nanobiosensors: A Platform for the Diagnosis of Microbial Pathogens
10.1 Introduction
10.2 Microbial Pathogens
10.3 Diseases Caused by Pathogens
10.4 Importance of Pathogen Detection or Disease Diagnosis
10.5 Biosensors
10.6 Nanobiosensors as Diagnostic Platform
10.7 Stabilization of Biomolecules with Nanoparticles
10.8 Types of Nanoparticles Used in Biosensor Development
10.9 Challenges and Future Prospects
Conclusion
References
11 Micro/Nanofluidics-Integrated Biosensors for Respiratory Viral Diseases Diagnosis
11.1 Introduction
11.2 Common Respiratory Viruses and Their Detection Components
11.3 Biosensors
11.4 Fluidic Technology
11.5 Applications of Micro/Nanofluidic-Based Biosensors in Respiratory Virus Detection
11.6 Advantages of Micro/Nanofluidic Diagnosis Tools Over the Other Diagnostic Methods
11.7 Conclusion and Future Perspectives
References
12 Nanobiosensor System: A Robust Analytical Tool for Pandemics
12.1 Introduction
12.2 Nanobiosensors for Global Pandemics
12.3 Nanobiosensors for COVID-19
12.4 Nanobiosensors for Influenza
12.5 Nanobiosensors for MERS
12.6 Nanobiosensors for HIV/AIDS
12.7 Nanobiosensors for Other Human Viruses
12.8 Selection and Optimization of Nanomaterials for Nanobiosensors
12.9 Current Challenges and Prospective Solutions
12.10 Conclusion
References
13 Biosensing Technologies to Improve Neurological Disease Management
13.1 Introduction
13.2 Trends, Challenges, and the Disease Burden
13.3 CNS Diseases
13.4 Utility of Neurobiosensors
13.5 The Technology Behind Biosensor Development
13.6 Clinical Applications
13.7 Conclusion
References
14 Nanotechnology-Based Strategies for Improvement of Disease Diagnostic Systems for Future Outbreaks
14.1 Introduction
14.2 Infectious Disease Outbreaks
14.3 Pandemic-Potential Priority Diseases for Future Outbreaks
14.4 Combating Infectious Diseases Through Diagnostics
14.5 Nanotechnology in Diagnostics
14.6 Conclusion
References
15 Biocompatibility and Toxicity of Nanomaterials in the Designing of Tools for the Diagnosis of Infectious Diseases
15.1 Introduction
15.2 An Overview of Nanomaterials in Infectious Disease Diagnosis
15.3 Biocompatibility Assessment
15.4 Mechanism of Nanoparticles in the Infectious Disease Diagnosis
15.5
In Vitro
and
In Vivo
Evaluation Methods of Biocompatibility Analysis
15.6 Toxicity of Nanomaterials
15.7 The Environmental and Health Hazards Caused by Nanoparticles
15.8 The Tools Developed for the Diagnosis of Infectious Diseases
15.9 Conclusion
References
16 Strengthening the Health System of the Communities in the Battle Against Infectious Diseases
16.1 Introduction
16.2 Primary Healthcare
16.3 Impact of COVID-19 on Infectious Diseases and Health Systems
16.4 Conclusion
References
Index
End User License Agreement
Chapter 2
Table 2.1 Here is an example of a table highlighting some key features and pro...
Table 2.2 A comprehensive table showcasing immunogenic proteins and potential ...
Table 2.3 A comprehensive table showcasing different types of immunomodulatory...
Table 2.4 An extended table showcasing 50 microfluidic devices used for detect...
Table 2.5 Here is a table showcasing 100 nanomaterials and their applications ...
Table 2.6 Here is a table showcasing 100 two-dimensional (2D) nanomaterials.
Chapter 3
Table 3.1 Recent reports on electrochemical biosensors for the detection of SA...
Chapter 4
Table 4.1 Table showcasing a selection of 50 nanobiosensors for diagnosing cor...
Table 4.2 Table showcasing a selection of 45 nanobiosensors for plant analysis...
Table 4.3 Table showcasing a selection of 45 examples of three-way junction sk...
Table 4.4 A selection of 49 SpACE-CCM biosensors for the detection of SARS-CoV...
Table 4.5 Wearable biosensor nano and microsystems with significant potential ...
Table 4.6 Biosensors’ signal amplification and transduction mechanisms.
Chapter 7
Table 7.1 Summarizing nanozyme-based detection of various pathogens and their ...
Chapter 8
Table 8.1 Table comparing catalytic biosensors and affinity biosensors.
Table 8.2 Comparison of label and label-free detection.
Table 8.3 Comparison of SPR and LSPR biosensors.
Table 8.4 Types of SPR techniques and their mechanisms of operation.
Chapter 11
Table 11.1 Microfluidic devices designed for the detection of SARS-CoV-2.
Chapter 12
Table 12.1 The advantages and disadvantages of different diagnostic methods ap...
Table 12.2 The summary of recently developed nanobiosensors, employed for the ...
Table 12.3 The summary of recently developed nanobiosensors, employed for dete...
Table 12.4 The summary of recently developed nanobiosensors, employed for the ...
Table 12.5 The summary of recently developed nanobiosensors, employed for the ...
Table 12.6 The summary of recently developed nanobiosensors, employed for the ...
Chapter 13
Table 13.1 Some commercially available biosensor platforms for the detection o...
Table 13.2 Variety of biomarkers and biosensors devised for neurological disor...
Table 13.3 Details of clinical trials for various biosensors for neurological ...
Chapter 14
Table 14.1 Summary of pandemics that took place worldwide.
Table 14.2 Advantages and disadvantages of LFAs. Adapted from reference [71].
Chapter 15
Table 15.1 Nanomaterials which are successfully incorporated with the biologic...
Table 15.2 The
in vivo
and
in vitro
assessment of the nanomaterials in the bio...
Chapter 16
Table 16.1 Community health systems before and after COVID-19 pandemic.
Chapter 1
Figure 1.1 The real-time acoustic detection of carcinoembryonic antigen with p...
Figure 1.2
S
cheme of a biosensor with an electrochemical transducer [14].
Figure 1.3 Schematic representation of glucose biosensing [10].
Figure 1.4 Different types of biosensors.
Figure 1.5 Event sequence in ‘second generation’ of mediator-based glucose bio...
Figure 1.6 (a) Redox mediators, (b) Direct electron transfer, and (c) [11] Amp...
Figure 1.7 Schematic of nanomaterial-modified electrode for glucose biosensor ...
Figure 1.8 Disposable strips of optical glucose biosensor and wearable electro...
Figure 1.9 Photonic hydrogel for continuous glucose monitoring by photonic hyd...
Chapter 3
Figure 3.1 (a) Design of a rapid electrochemical biosensor based on MXene/Pt/C...
Figure 3.2 (a) A surface molecularly imprinted electrochemical biosensor for t...
Figure 3.3 (a) Peptide nucleic acid and antifouling peptide based biosensor fo...
Figure 3.4 (a) An electrochemical biosensor for SARS-CoV-2 detection via its p...
Figure 3.5 (a) Ultrasensitive and amplification-free detection of SARS-CoV-2 R...
Figure 3.6 (a) Detection of SARS-CoV-2 in clinical and environmental samples u...
Figure 3.7 (a) An electrochemical PNA-based sensor for the detection of the SA...
Figure 3.8 (a) Detection of antibodies against SARS-CoV-2 Spike protein by scr...
Figure 3.9 CRISPR-Cas13a-powered electrochemical biosensor for the detection o...
Figure 3.10 (a) metal-organic-framework-nanohybrids for integrated point-of-ca...
Figure 3.11 Portable microfluidic impedance biosensor for SARS-CoV-2 detection...
Chapter 5
Figure 5.1 Voltammetric SARS-CoV-2 nucleocapsid antigen immunosensor.
Figure 5.2 ZIKV immunosensor diagram: (a) nanostructured electrode fabrication...
Chapter 6
Figure 6.1 Pathogen identification, detection, and quantification methods: (a)...
Figure 6.2 Diagram of a biosensor: (I) bioreceptor, (II) transducer, (III) sig...
Figure 6.3 Common types and materials of working electrodes used in electroche...
Figure 6.4 An intelligent potentiostat for fast quantification of SARS-CoV-2 s...
Figure 6.5 Illustrations of innovative biosensing platforms: (a) electrochemic...
Figure 6.6 (a) Timeline for nanobiosensor development. (b) Schematic overview ...
Figure 6.7 Illustration of the design of screen-printed electrodes (SPEs) modi...
Chapter 7
Figure 7.1 The schematic diagram of enzymatic nanobiosensor.
Chapter 8
Figure 8.1 Basic schematic diagram of a biosensor.
Figure 8.2 Basic schematic diagram of a SERS.
Figure 8.3 Basic schematic diagram of SPR biosensor.
Figure 8.4 Basic schematic diagram of LSPR biosensor.
Figure 8.5 Schematic representation of colorimetric biosensor.
Chapter 9
Figure 9.1 Illustration of adaptive conformational change. The K
F
represents t...
Figure 9.2 Basic steps of isolating aptamers using SELEX. Reprinted with permi...
Figure 9.3 Possible modification of short chain oligonucleotides. The figure w...
Figure 9.4 Principle of aptasensors. Aptamers fold into various tertiary struc...
Figure 9.5 Mechanisms of AuNPs-based aggregation aptasensors for the detection...
Chapter 10
Figure 10.1 Types of microbes.
Figure 10.2 Types of nanoparticles.
Figure 10.3 Development of nanobiosensors for diagnosis of microbial pathogens...
Chapter 11
Figure 11.1 Fundamental mechanism of biosensor.
Figure 11.2 Schematic diagram of a microfluidic chip.
Chapter 12
Figure 12.1 Multiple strategies to manage the global pandemics by utilizing na...
Figure 12.2 Chronological development of nanobiosensors for detecting and diag...
Chapter 13
Figure 13.1 Traditional vs. biosensor-based approaches for diagnosing neurolog...
Figure 13.2
Legend:
The figure depicts the four primary types of electrochemic...
Figure 13.3 Schematic of Optical Biosensors.
Legend:
The optical biosensor con...
Chapter 14
Figure 14.1 Interchangeable terms used to define a contagious disease in relat...
Figure 14.2 Conventional laboratories methods used for diagnosis of infectious...
Figure 14.3 Detection of TB antigens using LFAs. One line at the control (C) l...
Figure 14.4 Detection of SARS-CoV-2 using gold AuNPs-based in a solution. Repr...
Chapter 15
Figure 15.1 Most frequently used nanomaterials in the biomedical level with un...
Figure 15.2 Schematic illustration of antibacterial mechanism of NPs and the p...
Figure 15.3 Schematic representation of the interaction of the nanomaterials w...
Figure 15.4 Illustration shows the entry of a gold nanoparticle (in orange) wr...
Figure 15.5 The environmental and health hazards caused by the nanomaterials u...
Chapter 16
Figure 16.1 Strategies for strengthening public health systems.
Figure 16.2 Strategies for strengthening community health systems.
Cover Page
Table of Contents
Series Page
Title Page
Copyright Page
Preface
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])
Edited by
Suvardhan Kanchi
Dept. of Chemistry, CHRIST (Deemed to be University), Bengaluru, Karnataka, India
Ayyappa Bathinapatla
Dept. of Chemistry, CMRIT, Bangalore, India
Anitha Varghese
Dept. of Chemistry, CHRIST (Deemed to be University), Bangalore, Karnataka, India
and
Phumlane Selby Mdluli
Dept. of Chemistry, Durban University of Technology, Durban, South Africa
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-394-28766-6
Front cover art courtesy of Adobe Firefly and Wikimedia CommonsCover design by Russell Richardson
Welcome to Nano-Biosensor Technologies for Diagnosis of Infectious Diseases. This comprehensive volume explores the cutting edge of scientific innovation, presenting a curated collection of 16 meticulously crafted chapters that highlight the latest advancements in nano-biosensor technologies—a revolutionary approach to the diagnosis and management of infectious diseases.
Infectious diseases continue to pose significant global health challenges, underlining the critical need for rapid, accurate, and sensitive diagnostic tools. Situated at the intersection of nanotechnology and biomedicine, nano-biosensors offer unparalleled opportunities to meet these challenges by delivering highly sensitive and specific detection capabilities across various clinical settings.
Within these pages, readers will discover a treasure trove of cutting-edge research, ranging from foundational principles to practical applications. Authored by leading experts in the field, each chapter provides insights into current trends, emerging methodologies, and the innovative technologies that are driving the advancement of nano-biosensors for infectious disease diagnosis.
From innovative sensing mechanisms and fabrication techniques to their real-world implementation and clinical translation, this book offers a comprehensive overview of the current state of the art in nano-biosensor technologies. We hope this volume will serve as an invaluable resource for researchers, clinicians, policymakers, and anyone interested in leveraging the power of nanotechnology to combat infectious diseases and enhance global health outcomes.
We extend our sincere thanks to the contributors for sharing their expertise and insights, and to our readers, whose curiosity and commitment to advancing scientific knowledge propel progress in this vital field. Finally, our gratitude goes to Martin Scrivener and the team at Scrivener Publishing for their support in bringing this volume to light.
The Editors
January 2025
Mariyam Thomas1, Mathew George2, Derry Holaday M. G.3 and P. J. Jandas4*
1Department of Physics, St. Teresa’s College, Ernakulam, Kerala, India
2Department of Physics, Sacred Heart College, Kochi, Kerala, India
3Department of Chemistry, University of Calicut, Malappuram, Kerala, India
4iNest Bioincubation Centre, Dr. Moopen’s Medical College, Wayanad, Kerala, India
Fabrication and modification of biosensors is one of the extensively studied areas today due to viable manufacture methods with commercialization potential and excellent performance characteristics in terms of rapid detection, cost effectiveness, high selectivity, and sensitivity. Biosensors have already explored many applications including protein sensing-based disease identification, understanding the stages and medication. Advents in this area show biosensors have the potential to find application in next generation medicine like personalized drug delivery and error free biomarker detection with extreme selectivity and sensitivity. The book chapter summarizes the concept of biosensors, conventional classifications, application areas and potential as a dependable biomedical tool. A special emphasis is given into the recent advancements in biosensors used for glucose sensing. The important role of the nonmaterial-based transducing bioreceptors in a biosensor performance is also discussed in detail.
Keywords: Biosensors, biomarkers, bioreceptor, nanomaterials, SAW, QCM
Biological sensors, also called biosensors, are defined as analytical devices comprising a biological or biologically derived component [1] that decides their selectivity [2] capable of detecting an analyte [3] by the physiochemical component [2]. The real-time acoustic detection of carcinoembryonic antigen (CEA) was done using a bioreceptor of polyimide thin film doped with nanoparticles of Ti3C2Tx MXene-Au [13]. This work utilized thioglycolic acid arm linker mechanism. According to the immunoassay, biosensor response is linear to the concentration of CEA samples. Figure 1.1 represents the basic working principle of the CEA biosensor. The progress in the field of biosensors from the 1980s is immense with the development of life-essential devices such as pregnancy test kits which utilize biochemical or biological reactions.
Figure 1.1 The real-time acoustic detection of carcinoembryonic antigen with polyimide thin film doped with nanoparticles of Ti3C2Tx MXene-Au bioreceptor [13].
The basic component of a biosensor includes a biological recognition element which detects specific analytes, then the transducer which converts the corresponding biological signal to an electrical signal (Figure 1.2). This enables rapid, accurate detection and monitoring of samples from medical, food, agriculture, environmental, and industry-based resources. According to International Union of Pure and Applied Chemistry (IUPAC), a biosensor is “a device that uses specific biochemical reactions mediated by isolated enzymes, immune systems, tissues, organelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals” [4].
Figure 1.2Scheme of a biosensor with an electrochemical transducer [14].
The three major parts of every biosensor include [1]:
Biological recognition element that facilitates the device to recognize the target molecule from the other chemicals present and the binding is followed [
1
].
Signal conversion unit which is a transducer [
4
] that converts the specific binding process to a measurable signal [
1
].
A signal processing system that includes a detector [
5
] and the detected signal is converted into readable form [
1
].
Glucose biosensors dominate in the industry by covering about 85% [6] and the work on the principle is based on the detection of disease indicator analytes such as glucose and insulin [7]. The first biosensors were developed in the early 1960s by Dr. Leland C Clarkin where an enzyme electrode with glucose oxidase (GOD) was employed for the measurement of the concentration of glucose [4]. The GOD catalyzes the formation of gluconolactone. The proportional increase in hydrogen peroxide concentration to the glucose concentration during the oxidation of β-D-glucose and the decline in oxygen concentration is detected electrochemically [8]. Effective glycemic monitoring has been achieved ever since the introduction of glucose biosensors. These devices also have a place in various applications such as food analysis and bioprocess monitoring [9]. Though techniques like radio labelling prevail for the measurement, the complications in the procedure, the bulk size of the equipment, sample destruction, and low spatial resolution problems prompt us to look for an effective technique, and biosensors pave its importance in this scenario [7]. Continuous, real-time glucose concentration monitoring in liquid samples ranging in nanoliters is achieved through modern glucose biosensors which have miniaturized micro/nanoscale range sensors. These sensors achieve the measurement in single cells or isolated organelles because of their high spatial resolution [9].
Working Principle of Glucose Biosensor
The biosensor consists of a biological component that on specific binding produces a response which is transmuted into a quantifiable signal with the help of a transducer [2]. The basic classification of biosensors is given in the Figure 1.4. Most prevailing glucose biosensors have better sensitivity, reproducibility, and easy maintenance, are economical in nature, and are electrochemical in type. Generally, glucose measurements are based on either of the enzyme interactions viz hexokinase, glucose oxidase (GOx), or glucose-1-dehydrogenase, of which GOx is considered superior due to its immense selective nature. Moreover, it is easily available and can withstand extreme temperatures, pH conditions, and ionic strength compared to other enzymes. Figure 1.3 represents the catalysis process by immobilized glucose oxidase. In the process, flavin adenine dinucleotide (FAD) acts as a redox cofactor for the oxidation of β-D-glucose employing molecular oxygen, thus converting it into gluconic acid and peroxide (Figure 1.3). The mechanism of the process is shown in Scheme 1.1.
The FAD on reduction converts to FADH2. Upon oxidation, H2O2 is formed which is oxidized at platinum electrode. It detects the electron transfer number thus detecting the concentration of glucose in the sample.
Figure 1.3 Schematic representation of glucose biosensing [10].
Scheme 1.1 Mechanism of the glucose detection.
Figure 1.4 Different types of biosensors.
When glutamate dehydrogenase (GDH) with nicotinamide-adenine dinucleotide (NAD) is the cofactor, NADH is produced in the place of H2O2 [14].
Evolution in Biosensor Technology
A wide variety of biosensor availability is seen today as the principle of working of biosensors is getting changed over the years.
1) First Generation Glucose Biosensors
The first proposed biosensor includes an oxygen electrode, GOx thin layer, semipermeable oxygen inner membrane, and an outer dialysis membrane. Natural oxygen substrate-based biosensors come under the first generation for the detection of the hydrogen peroxide produced as the process is simple but requires higher operation potential for high selectivity. The variation of the O2 tension due to less solubility O2 in biofluids is another drawback of these biosensors [1].
1.1) Electroactive Interferences
The hydrogen peroxide amperometric measurement at common working electrodes requires a relatively high potential. The co-existing [9] reducing species [11] like ascorbic acids, uric acids or acetaminophen may interfere and affect the selectivity and sensitivity of the process. Moreover, other components existing in the sample which can undergo oxidation will also affect the accuracy.
To avoid this, attempts towards reduction of access to the surface of electrodes were made by using selective coating with multi and mixed polymer layers [9]. Their transport properties based on charge, size, or polarity can block the electroactive compounds and surface-active macromolecules. The surface is thus protected which results in higher stability. High selectivity is shown by electro-polymerized films, polyphenol, and over-oxidized polypyrrole by confining GOx onto the surface [11]. Multi-(overlaid) layers that have combining properties of different films can be used for additional advantages, i.e., the intervention of neutral acetaminophen and negatively charged ascorbic and uric acid were eliminated by simultaneous alternate deposition of cellulose acetate and Nafion [9]. The use of metalized carbon transducers (Rh-C or Ru-C) also offers high selectivity through determining H2O2 at an optimal potential range of 0.0 V. The surface metal oxide film is converted to free metal using H2O2. An anodic current signal is produced when it is reoxidized electrochemically. By including a discriminative layer with metal to a Nafion film, additional improvements can be made. Horseradish peroxidase (HRP) is an enzyme that catalyzes peroxide oxidation thus offering a low potential selection detection of the GOx-generated H2O2. The carbon nanotube (CNT)-modified electrodes offer high selectivity towards glucose detection. On coupling CNT with platinum nanoparticles shows high efficiency as it has enhanced sensitivity and speed [11].
1.2) Oxygen Dependence
The errors due to the oxygen deficit prevailed in devices based on oxidase as they use oxygen as physiological acceptor of electrons. These errors result in the reduced upper limit of linearity. When normal O2 concentration is lower, around 1 order of magnitude than the physiological level of glucose points out oxygen deficit. This constraint can be overcome by applying mass transport limiting films. Their usage will enhance the flux of the O2 and glucose permeability ratio [11].
2) Second Generation Glucose Biosensors
2.1) Electron Transfer between GOx and Electrode Surfaces
The second-generation glucose sensors, redox mediators, replace oxygen. The transfer of electrons from enzymes to the surface of the working electrode will lead to further improvements [1].
Scheme 1.2 Mechanism of synthetic mediators electron transfer process, where M(ox) and M(red) are the oxidized and reduced forms, respectively.
Figure 1.5 Event sequence in ‘second generation’ of mediator-based glucose biosensors [11].
2.2) Use of Non-Physiological Electron Acceptors
The synthetic mediators transport the electrons from the FAD center to the electrode surface, as shown in Scheme 1.2.
A current signal is produced when the reduced form is reoxidized at the electrode, regenerating the mediator’s oxidized form. This is shown in Figure 1.5 [11].
Ferrocene, ferricyanide, quinines, tetrathiafulvalene (TTF), tetracyanoquinodimethane (TCNQ), thionine, methylene blue, and methyl viologen are some of the electron mediators which can improve the sensor performance. The advantages of ferrocenes include ferrocenes inertness towards oxygen, stability in both oxidized and reduced states, resilience across a wide range of pH levels, reacting rapidly with enzymes, and showing electron transfer kinetics [1], which enables them to perform effectively. The oxidation of endogenous species cannot be completely removed but minimized by low potential of most mediators. Further, additional errors will be led by consumption of mediators. For an extended continuous operation, mediated systems display low stability [11].
2.3) Wired Enzyme Electrodes
A redox polymer, coupled with enzyme wiring, enhances electrical conductivity between the redox center of GOx and electrode surfaces. Establishing a communication link between GOx and electrodes is the base of a non-diffusional route of biosensing. This connection is achieved by tethering the enzyme to the surface using a long, flexible, hydrophilic polymer backbone.
To accomplish this, a dense array of covalently bonded osmium-complex electron relays, such as poly(vinylpyridine) or poly(vinyl imidazole)] are used. This arrangement forms a three-dimensional network that attaches to the surface, minimizing the distance between redox centers and FAD center of the enzyme. Electrons from the redox site of GOx are transported through the gel polymer network to the electrode, providing high current outputs, rapid response times, and stabilizing the mediator to the surface. Ultra small enzyme electrodes can be used with the aid of huge current densities. Wired enzyme electrons are thus particularly attractive for in vivo applications [11].
Main advantages are high current outputs, fast response, and stability. Ultra-small enzyme electrodes can be used with the aid of huge current densities. Wired enzyme electrons are thus particularly attractive for in vivo applications [11].
2.4) Modification of GOx with Electron Relays
Another approach to facilitate electron transfer between the GOx and the electrode surface involves chemically altering GOx with electron-relay species. The flavin center of GOx undergoes oxidation due to the covalent attachment of the ferrocene group and results in electron tunneling in a number of consecutive steps. Enzyme reconstitution process improves the efficiency of electrical communication with electrodes in the glucose bio-sensors. The fitment of electron-transfer relays at the boundary of enzymes is also considered in the case of short electron-transfer distances [11].
2.5) Nanomaterial Electrical Connectors
The application of nanomaterials in bioanalytical chemistry is a vast field. Nanomaterials offer an effective means for wiring redox enzymes, such as GOx, to electrodes. Gold nanoparticles and CNTs serve as efficient electrical connectors between the electrode and the redox center of Gox (Figure 1.6) [13]. Utilizing a dithiol linker, gold nanoparticles are immobilized onto the gold electrode, acting as nano plugs for electrical wiring to the redox-active center of GOx. This will result in a high electron-transfer turnover (around 5000/s). Moreover, additional nanomaterials can be tethered to enzymes via CNTs, facilitating favorable surface orientation and serving as electrical connectors between their redox center and the electrode surface. The activation of GOx by these requires over potential and this can be reduced, enhancing the contact between nanomaterials and the electrode [11].
Figure 1.6 (a) Redox mediators, (b) Direct electron transfer, and (c) [11] Amperometric enzyme electrodes [10].
3) Third Generation Glucose Biosensors
They operate without reagents or mediators, utilizing a low potential similar to that of the enzyme’s redox potential [11]. It is based on the enzyme’s active site enabling direct transfer of an electron from glucose to the electrode [11]. Highly toxic mediators are avoided [1] due to very low operating potential and high selectivity is ensured [11]. Only few enzymes peroxidases [1] have been reported that can enable an effective electron transfer at conventional electrodes. Studies were done for new electrode materials as attempts for direct electron transfer of GOx to conventional electrons were futile.
The newly customized optimally designed electrode ensures minimal electron-transfer distance between the immobilized protein and the surface. One approach is by creating third-generation amperometric glucose biosensors utilizing conducting salt electrodes with charge-transfer complexes like TTF-TCNQ [11]. These complexes can facilitate the electrochemistry of pyrrole-quinoline quinone enzymes (GDH-PQQ) and flavoproteins (GOx) [1].
Classification of Glucose Biosensors and Their Properties
1) Based on Transducing Element
1.1) Electrochemical Glucose Biosensors
Detection of the electrochemical signal during a bio-interaction process is the basic working principle of electrochemical biosensors. Detectors can be classified into potentiometric, amperometric, or conductometric types based on their mechanism. The potentiometric sensor measures change in the charge density at the surface of the electrode and amperometric biosensor measures current liberated as a result of transfer of electrons between a biological system and electrode. The change in ionic conduction between metal electrodes is measured by the conductometric sensors. Miniaturization and simplification of the system are achieved by integrating an immobilized enzyme complex with an electrochemical sensor, thus enabling reagent-less glucose analysis. Modification of the working electrode with various nanomaterials is one of the current developments in glucose biosensors and is depicted in Figure 1.7. Nanomaterials possess unique characteristics, including a large surface area for enhanced reaction activity, excellent catalytic efficiency, and strong adsorption capabilities. This enables them to work as a matrix to modify the electrode surface. This also provides enzyme immobilization biocompatible areas.
Figure 1.7 Schematic of nanomaterial-modified electrode for glucose biosensor cinnamic acid diazonium salt, which, in electrochemically reduced form, is used as the immobilization matrix for the glucose biosensor [15].
The attachment of other biological agents are achieved by modifying the glassy carbon electrode (GCE) with the cinnamic acid group. Miniaturization is accomplished by attaching the enzyme to the self-assembled oligophenylethynylenethiol monolayer, serving as a crosslinker for immobilizing glucose oxidase to the gold electrode [7]. Out of the three most commonly used enzymes for glucose detection, i.e., hexokinase, glucose oxidase (GO), and glucose-1-dehydrogenase, glucose oxidase (GOx) is widely regarded as a standard enzyme for biosensors because of its high selectivity, affordability, and capacity to endure elevated pH levels, temperatures, and ionic strengths. When glucose dehydrogenase is used instead of GO, amperometric biosensing of glucose can also be carried out. Mediators, which are carriers that can be biologically active or synthetic, are used to enhance the connection between the redox enzymes and electrodes [7].
1.2) Optical Biosensors
Figure 1.8 Disposable strips of optical glucose biosensor and wearable electronic devices [16].
Another way for glucose sensing includes the utilization of optical properties of compounds with intrinsic fluorescence and their coenzymes. This type of biosensor undergoes changes in its spectral properties when the binding of enzyme takes place. After the binding of the enzyme with the glucose, the fluorescence intensity change is seen for the protein part of the enzyme but no associated change is seen in the absorption spectra of the same. Co-enzymes can contribute to absorption and luminescence changes due to its interaction with glucose. The utilization of oxygen upon the interaction of the enzyme is measured to determine the glucose concentration using probes [7]. Nano/microscale device plays remarkable impacts in developing sensitive visualization assays, low-cost analyses, and home tests of diabetics (Figure 1.8).
Fluorescent-based glucose sensing is an exceptionally sensitive technique for detecting glucose at the molecular level. The sensing schemes include enzymes which include plant lectin, bacteria, or intrinsic cellular fluorescence. The smaller size of probes such as dyes and quantum dots enables biofunctionalization through diffusion rather than endocytosis.
Fluorescent probes are remotely interrogated using an external UV excitation source, and are capable of penetrating tissues to a depth of centimeters. This results in specific and configurable photoluminescence in quantum dots and dyes. Förster resonance energy transfer (FRET) is the key process behind the photoluminescence behavior. Notably, observations are made without interference from light scattering in tissues, and corrections are applied for errors due to photobleaching or fluorophore degradation.
Furthermore, FRET-based biosensors offer spatial resolution of target analytes, as the decay time of acceptor/donor fluorophores depends on the distance as 1/R6. When fluorophore-to-fluorophore distances reach above 10 nm, FRET signals attenuate rapidly. For non-invasive, in vivo sensing, and continuous monitoring, fluorescent-based glucose sensors are highly advantageous. Additionally, optical glucose sensors can accurately measure fluctuations in glucose level and associated biochemical pathways, including feedback cascade involving glucose catabolism, adenosine triphosphate (ATP) production and other biological processes [9].
A novel optical Prussian blue (PB)-based biosensor is developed which can detect H2O2. It evaluates the pH and acts as an optical transducer in pH-based biosensors. The redox species are detected based on the color change on its reduction. The used film is then renewed on introducing it to a flow injection system. The film system serves as the transducer for optical biosensors. The modified reduced film, combined with glucose oxidase, forms the basis of an optical biosensor. This type is mainly used for the glucose determination in urine samples. This sensor used for the determination of glucose in soft drinks is an optical fiber biosensor. Electroluminescence is the basic working principle of such sensors where the glucose oxidase is immobile on GCE surface. Recently, Haider et al. developed a hydrogel sensor based on phenylboronic acid (PBA) containing photonic nanostructures for swift and continuous glucose quantification. This sensor incorporates photonic nanostructures imprinted on the PBA-based hydrogel. It is comprised of three variations: free-standing (FS), stand-alone (SA), and optical fiber (OF) sensors, each capable of measuring glucose concentrations within the range of 0–50 mM (Figure 1.9).
The direct determination of glucose concentration from the blood samples is possible with a reagent-less reversible biosensor. The envelopment of glucose oxidase and peroxidase within a polyacrylamide polymer gel forms the basis of a reagent-less and reversible biosensor, utilizing its intrinsic spectroscopic properties. The water-diluted blood sample is introduced into the sensor working in a continuous mode. Here the concentration of glucose is measured with an optical fiber grating, where the absorbance of glucose and the wavelength used are in resonance. This method has better sensitivity and reproducibility.
Biosensors to detect glucose in other biological fluids in micro level concentration are in the developmental stage. The compounds with the ability to intercalate metal atoms and ions like molybdenum disulfide (MoS2) is a good candidate but its poor solubility reduces the electrochemical device performance. This is rectified by using conductive additives like silver and the electrochemical performance is improved [7].
Figure 1.9 Photonic hydrogel for continuous glucose monitoring by photonic hydrogel with a smartphone readout [17].
2) Based on Clinical Application
2.1) Continuous Glucose Monitoring Biosensors
Self-testing represents a significant advancement in biosensing; however, it encounters limitations when numerous tests are required within a short timeframe. Continuous glucose monitoring (CGM) addresses this challenge by providing a continuous and valid response. The CGM biosensors necessitate biocompatibility, miniaturization, stability of enzymes and transducers, oxygen supply, safety, convenience, and in vivo calibration. Two primary systems are employed for continuous monitoring: subcutaneous and blood glucose levels. Nonetheless, these systems have drawbacks such as thromboembolism and surface contamination of electrodes by proteins [7].
2.1.1) Implantable Glucose Biosensor
Nowadays, this method is used for CGM which has a prolonged stability. Here, glucose undergoes oxidation by reacting with molecular oxygen in the presence of GO to form gluconolactone and H2O2. Electrochemical detection of concentration of H2O2 is done and proportional to corresponding glucose concentration. Electrochemical oxygen reduction on the Pt electrode will result in an amperometric signal by which oxygen can be detected. An oxygen-permeable and glucose-diffusive membrane is employed to avoid the mass transfer of oxygen and glucose. A hydrophobic, oxygen-permeable membrane is employed to segregate physiological fluid components from the working electrode surface, reducing interference. Enzyme immobilization enhances biosensor stability, although long-term operational stability remains a significant drawback. The lifespan of biosensors can be widened by supplementation of the immobilized compound with a fresh enzyme. A glucose sensor with GO immobilized on fine graphite powder which is implantable can be fabricated. When the enzyme activity decreases, the graphite enzyme in the fluid state is recharged, thus, improving the lifetime of the detector. A highly permeable hydrophobic membrane is employed for the electrode such that the required amount of oxygen is assured and peroxide detection is done by a platinum electrode [7].
2.2) Non-Invasive Glucose Monitoring Systems
This class of biosensors are of particular interest among other varieties. The wearable glucose monitor utilizes electro-osmotic measurement to accurately assess extracted glucose levels which is clinically acceptable. Noninvasive glucose concentration measurement is achieved through a metal oxide gas sensor, which detects the concentration of gas in the exhaled air. The exhaled air is carbon dioxide, but in the case of diabetic patients, certain amounts of volatile organic solvents like acetone also expired along with the carbon dioxide. This exhaled air is fed into the input chamber with a sensor detection system. The sensor detects variations in conductivity when exposed to oxidizing and reducing agents. The result is typically in the form of voltage or resistance and depends on the type and concentration of volatile organic solvents present [7].
A flexible three-dimensional glucose biosensor has been developed for continuous electrochemical glucose monitoring from human tears. The sensitivity is improved by enhancing the electrode surface area through three-dimensional micropatterning of the electrode. By immobilizing GO onto this three-dimensional electrode, properties such as good repeatability and fast response for low-level concentration of glucose are achieved. The future of diabetes management lies in continuous and real-time glucose monitoring, enabled by non-invasive electrochemical epidermal glucose monitoring systems that allow for patient self-monitoring [7].
3) Nanobiosensors: Based on the Type of Nanoparticles
Nanotechnology created advancements in biosensor technology with improved and enhanced characteristics. There are three major groups of glucose-sensing molecules. They include GO, glucose-binding proteins, and glucose-binding small molecules. The advanced biosensors are developed with nanoparticles coupled with glucose-detecting molecules where the nanoparticles act as the transducers. Nanoparticle-based sensors exhibit easy absorption and improved performance due to their characteristics such as high surface-to-volume ratio. The distance between the enzyme and electrode and the rate of electron transfer are inversely related. Improvements in specificity, selectivity, reproducibility, and reliability is another advantage due to the application of nanomaterial. Nanomaterials of different morphology such as magnetic beads, quantum dots, tubes, wires, rods, fibers, composites, films, polymers, and plates are suitable for glucose detection because of their unique physical, chemical, magnetic, and optical properties [7].
3.1) Metal Nanoparticles
This type of sensor offers a lower limit of detection [12]. The blood glucose is monitored by the GO enzyme. When the enzyme comes into contact with FAD, which is embedded in a protective protein shell, it becomes active. Flavin adenine dinucleotide (FAD) is functionalized with gold nanoparticles to enhance the interaction between the active site and the electrode. Immobilizing the enzyme on gold nanoparticles helps prevent leakage due to its strong adsorption properties, thus increasing stability. A biocomposite film, which is electrochemically deposited on the gold electrode composed of chitosan, gold nanoparticles, and glucose oxidase, exhibits high stability [7].
Another fabrication technique for glucose sensors involves the covalent attachment of GO to a gold nanoparticle monolayer-modified gold electrode. The gold nanoparticles on the biosensing interface enhance electron transfer. Recent studies explored the immobilization of GO on a graphite rod modified with gold nanoparticles, investigating its impact on amperometric sensors. This approach has the potential to significantly increase the electron transfer rate.
3.2) Magnetic Nanoparticle
Their biocompatibility, low toxicity, and superparamagnetic properties make Fe2O3 nanoparticles an excellent choice for immobilizing carriers in biosensors. One method involves creating a nanocomposite-based biosensor on an indium tin oxide (ITO) glass plate by dispersing Fe2O3 nanoparticles in a chitosan solution, followed by the physical adsorption of GO onto the film. Another type of biosensor employs a film made of C/NiFe2O4 nanoparticles, where GO is immobilized within the chitosan/NiFe2O4 nanoparticle matrix. Electrodes modified with C/NiFe2O4 NPs/ GO show exceptional electrocatalytic responses for glucose oxidation [7].
3.3) Nanofiber
Nanofibers when coupled with conductive nanomaterials are capable of exhibiting good sensor performance under their distinct electronic, magnetic, and optical properties. Carbon nanomaterials play a significant role in sensor application as they are easily functional, biocompatible, conductive, and has a large surface area. The whole surface area of carbon nanofibers can be activated as they have cylindrical nanostructures with graphene layers arranged as stacked cones. They act as both an immobilization matrix for biomolecules and transducers. Studies indicate that carbon nanotube-based biosensors exhibit increased sensitivity and improved stability. These biosensors are fabricated through the direct immobilization of enzymes onto the surface of carbon nanofibers. Electrochemical amperometric bienzymatic glucose biosensors are constructed by co-immobilizing HRP and GO on vertically aligned carbon nanofibers, enabling higher detection limits. Highly flexible structured nitrogen-doped carbon nanofibers (NCNFs) can be employed for electrode modification.
The NCNFs were seen to have greater surface area and electron transfer when compared with carbon nanofibers. An increased lifetime is the main advantage of electrospun nanofibers and hence their fusion and integrated nanomaterials will be excellent in sensor fabrications [7].
3.4) Nanorod-Based Biosensors
Zinc oxide (ZnO) is a potential candidate for electrochemical sensor fabrication as it is highly compatible and has high oxygen affinity. Electrochemical biosensors based on ZnO nanorods are economical, authentic, fast, and harmless. The electrochemical reaction between ZnO nanorods and glucose is the basic mechanism of this sensor. A sol-gel derived ZnO nanorods-based electrochemical sensor has been recently developed which offers advantages that include cost-effectiveness, accuracy, fast response, and high sensitivity. Moreover, hydrothermal growth is adopted for the synthesis of ZnO nanorods which is easy, cheap, and requires low growth temperature. The length of synthesized ZnO nanorods is controlled by factors like growth time and temperature.
The morphology of synthesized nanorods is influenced by the homogeneity of the growth solution. An electrochemical sensor has been fabricated using an ITO glass substrate coated with a titanium layer as the working electrode and platinum as the reference electrode. Spin coating with a thin membrane of Nafion enhances enzyme leakage and stability of the working electrode. Recently, a nonenzymatic fluorescent biosensor has been developed for the direct detection of glucose concentration. This biosensor utilizes immobilized ZnO nanorods The detection mechanism relies on the photoluminescent quenching of ZnO under UV irradiation [7].
3.5) Nanowire
The electrochemical deposition of ZnO nanowires on an Au-coated polyester substrate results in an enzymatic glucose sensor. Glucose oxidase is immobilized on zinc oxide nanowires by a simple physical adsorption method. An amperometric glucose biosensor has been developed using a film composed of silver nanowires and chitosan-glucose oxidase. This bio-sensor exhibits excellent selectivity, high response, and stability. Detection of glucose from serum is possible by employing this biosensor [7].
3.6) Nanocomposite
For the sensor fabrication, different forms of nanocomposites are widely used. Nanofilms, nanotubes, and nanowires are some of them. The glucose biosensor constructed by electrodeposition of palladium nanoparticles and GO onto Nafion-solubilized carbon nanotubes has increased storage time and decreased interference and performance. This is because the ability of biocatalysis is retained and the oxidation and reduction process will carry out effectively. An amperometric biosensor with the immobilization of GO onto a gold and platinum nanoparticle-modified CNT electrode exhibits good electrocatalytic activity and shows a rapid response to glucose. An electrode coated with Nafion avoids the loss of GO and eliminates interference [7].
The non-enzymatic glucose biosensor measures accurately and precisely the glucose level in real samples of blood. This biosensor works in alkaline media with Cu nanoclusters that are electrochemically deposited on a multi-walled carbon nanotube (MWCNT)-modified glassy carbon electrode. As electrocatalytic activity toward oxygen reduction is larger for bio-derived nanocomposite metal protein platinum-bovine serum albumin nanocomposite, it is used in an electrochemical sensing matrix for glucose determination. Such sensors have very good selectivity and storage stability. Also, it can be applied in real serum samples [7].
3.7) Quantum Dots-Based Biosensor
Broad absorption, narrow emission, and high quantum yield are some of the unique characteristics of semiconductor quantum nanoparticles-based biosensors. A hybrid quantum dot (QD) is electrodeposited onto the pencil graphite electrode surface and glucose dehydrogenases are immobilized onto the QD-modified electrode. This electrode has wide application in the photoelectron chemical determination of glucose by these modified electrodes and have wide applications on flow injection analysis systems. The peculiarities such as simplicity in design, easiness in integration, and portability, make them apt for conducting real sample analysis.
There are three steps by which photochemical biosensors can be fabricated. They are QD immobilization into an electrode, electrode surface illumination, and photocurrent generation due to photoexcitation of semiconductor QDs based on the analyte in supporting electrolyte. Various QD ligand systems are also taken as biosensing elements. Bioconjugated fluorescent quantum dots increase the lifetime and thus fluorescence detection is improved. Multilayered QD films of cadmium telluride (CdTe) and graphene oxide-based biosensor have been fabricated recently using a layer-by-layer assembly technique. Quenching of the photoluminescence of QDs in the film occurs when it comes in contact with the glucose solution, which is directly proportional to the glucose concentration. A potentiometric glucose biosensor, which is highly sensitive, is fabricated using functionalized indium nitride (InN) QDs, which has unique properties that include high surface charge density and robust surface properties. The sensitivity of the electrochemical response of enzymes-coated on InN QDs is high [7].
3.8) Carbon Nanotube-Based Biosensors
Carbon nanotubes (CNTs) have astonishing electrical properties which can be utilized for the fabrication of biosensors. There are two types of CNTs, they are, single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs). Rolling a single graphite sheet into a tube results in SWCNT, while MWCNT has many layers of concentrically arranged graphite sheets. The MWCNTs have more electrical conductivity compared to SWCNTs. The combination of MWCNT, graphite powder, and glucose oxidase freeze-dried powder in a glass capillary is fabricated to form a real-time monitoring needle-like glucose biosensor with required stability. The electrochemically obtained resultant output measures the presence of glucose and H2O2. When platinum nanospheres are included in carbon nanotube-based biosensors, electrochemical performance can be improved as the glucose sensitivity is enhanced. Amperometric CNT/ GO-based biosensors can be fabricated and the electrode surface can be modified with a Nafion, a perfluorosulfonate polymer that has the ability to solubilize CNT. Highly sensitive (picomolar sensitive) enzyme-free displacement-based chemiresistive biosensors with SWCNT can selectively identify glucose and the detection of glucose is based on the displacement of a plant lectin-like concanavalin-A, bound to a polysaccharide dextran immobilized on SWCNT [7].
3.9) Graphene-Associated Biosensors
The distinct properties of graphene such as economic availability, improved area of surface, and easy to process, making them the best choice to apply in the scientific and technological field. Reduction of graphene oxide for functionalized graphene sheets which exhibit sufficient structural defects and functional groups and excellent electrochemical properties. Graphene possesses a high electron density across a broad energy range, owing to its exceptional electron-transferring capability. Solution-gated graphene transistors play a significant role in real-time, high-throughput, and low concentration glucose detection, which distinguishes them from other sensors [7].
Home Testing of Blood Glucose
The personal/home glucose testing has paved the way for simple blood sugar testing. Blood glucose home testing devices should be of the best quality as they may be used daily for diagnosis. The major part of a personal blood glucose monitor is ready-to-use test strips on which the electrodes are screen-printed. They are bulk manufactured using processes like thick film micro-fabrication or vapor deposition process. Here, a patterned mask is produced by printing patterns of conductors and insulators to the plane substrate surfaces. Each strip is coated with the necessary electrodes and membranes by employing ink-jet printing technology and as a result, the reagents are easily dispensed and dry-coated. The surfactants coated on the strip ensure a uniform sample coverage and separation of the blood cells. These devices have several advantages: elimination problems of carryover, low cost, and the possibility of their mass production. A sophisticated device is inevitable for assuring accurate test results. The control meters are small, easy to carry, and battery-operated. The advantages of modern glucose biosensors include extended memory capacity and computer downloading capabilities, the disadvantages include home low and irregular testing frequency, lack of knowledge to interpret the test results by the user and liability problems. Enhanced devices with integrated devices, offering multifunctional capability, and more convenience are the properties expected as the future of these devices [11].
Challenges and Future Scopes
Glucose sensing technology has taken decades to evolve to mature and become established in the market. The limits of technology are seen when the glucose sensors are actually put into practice for glucose detection in blood or any other invasive fluids. Intervention of different molecules, i.e., lactate and urea, during the optical evaluation of glucose in interstitial fluids as this will reduce the reliability of results. Analytical inaccuracy due to device miniaturization is another drawback of glucose detection in noninvasive fluid sampling. Further improvements are required in the fields of sensitivity of sensors. Moreover, the evolution of superior algorithms to convert signal data into corresponding glucose levels. Another alarming challenge regarding glucose biosensing is the nondestructive usage of bio-fluids and if it is possible, it will be a promising option for future directions and have a positive impact on the healthcare system [12].
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