Electronic Devices, Circuits, and Systems for Biomedical Applications: Challenges and Intelligent Approach

By Valentina Emilia Balas

Electronic Devices, Circuits, and Systems for Biomedical Applications: Challenges and Intelligent Approaches explains the latest information on the design of new technological solutions for low-power, high-speed efficient biomedical devices, circuits and systems. The book outlines new methods to enhance system performance, provides key parameters to explore the electronic devices and circuit biomedical applications, and discusses innovative materials that improve device performance, even for those with smaller dimensions and lower costs. This book is ideal for graduate students in biomedical engineering and medical informatics, biomedical engineers, medical device designers, and researchers in signal processing.

• Presents major design challenges and research potential in biomedical systems
• Walks readers through essential concepts in advanced biomedical system design
• Focuses on healthcare system design for low power-efficient and highly-secured biomedical electronics

• Language: English
• Publisher: Academic Press
• Release date: Apr 28, 2021
• ISBN: 9780323853699

Book preview

Electronic Devices, Circuits, and Systems for Biomedical Applications

Challenges and Intelligent Approach

Editors

Suman Lata Tripathi

Valentina E. Balas

S.K. Mohapatra

Kolla Bhanu Prakash

Janmenjoy Nayak

Table of Contents

Cover image

Title page

Copyright

Contributors

Preface

Chapter 1. Carbon-based electrodes as a scaffold for the electrochemical sensing of pharmaceuticals: a special case of immunosuppressant drugs

1. Introduction

2. Carbon materials used for electrode modifications

3. The electroactive immunosuppressant drugs

4. Bare carbon electrodes as a platform for the electroanalysis of immunosuppressant drugs

5. Electroanalysis of immunosuppressants on modified carbon electrodes

6. Electrochemical biosensors for immunosuppressants using carbon electrodes

7. Conclusion and outlook

Chapter 2. Selenium-based amorphous semiconductors and their application in biomedicine

1. Introduction

2. Defects in selenium

3. Optical analysis

4. Electrical analysis

5. Synthesis of selenium nanoparticles (SeNPs)

6. Applications of SeNPs for biomedical purposes

7. Conclusion

Chapter 3. Nanodevices for biomedical applications

1. Introduction

2. Nanodevices in implantable devices

3. Nanodevices for IMD memories

4. Nanodevices for wireless power systems

5. Nanodevices for temperature sensors

6. Nanodevices for image sensors

7. Applications of image sensors in biomedicine

8. Conclusion

Chapter 4. Analytical model and sensitivity analysis of a gate-engineered dielectric modulated junctionless nanowire transistor-based biosensor

1. Introduction

2. Device structure

3. Development of analytical model

4. Simulation setup

5. Results and discussion

6. Conclusion

7. Appendix A

8. Appendix B

9. Appendix C

Chapter 5. Design and development of AlGaN/GaN HEMT for biosensing applications for detection of cancers, tumors, and kidney malfunctioning

1. Introduction

Chapter 6. Preprocessing of the electrocardiogram signal for a patient parameter monitoring system

1. Introduction

2. Biomedical signals

3. Artifacts associated with electrocardiogram signals

4. Adaptive filters for noise cancellation

5. Patient parameter monitoring system

6. Summary

Chapter 7. A study on sleep stage classification based on a single-channel EEG signal

1. Introduction

2. Methodology

3. State-of-the-art analysis based on automated sleep scoring

4. Results and discussion

5. Conclusion

Chapter 8. Implementation of ultra-low-power electronics for biomedical applications

1. Introduction

2. Related work

3. Sensors

4. Sensing techniques

5. Wireless remote sensing technology

6. Method initiation with improved techniques

7. Conclusion

Chapter 9. Sensors and their application

1. Introduction

2. Types of sensors

3. Application of the sensors

4. Enabling sensors with IoT and machine learning

Abbreviations

Chapter 10. ADC and DAC for biomedical application

1. Introduction [1,2]

2. Analog-to-digital conversion [1–4]

3. Data converter parameters

4. Data converter architectures [1,5–7]

5. ADC application in biomedical electronics

6. Conclusion

Chapter 11. A low-power reconfigurable ADC for bioimpedance monitoring system

Pipe line analog to digital converter

2. Pipelined ADC architecture

3. Automatic adaptation unit

4. DTMOS logic

5. Simulation results of the designed circuitry

6. Performance

7. Conclusion

Chapter 12. Design of a 16-bit 500-MS/s SAR-ADC for low-power application

1. Introduction

2. Overview of analog-to-digital converters

3. Successive approximation register

4. Proposed SAR-ADC design

5. Conclusion

Chapter 13. Design and applications of rail-to-rail FC-OTA and second-generation CCII+ cell

1. Introduction

2. Circuit schematic and description of low-voltage, low-power FC-OTA

3. Simulation results of OTA

4. Second-generation current conveyor (CCII)

5. Applications of operational transconductance amplifiers

6. Applications of second-generation positive CCII cell

7. Conclusions

Chapter 14. The role of electronic filters in biomedical applications: a brief survey

1. Introduction

2. Literature review

3. Conclusions and future scope of work

Chapter 15. Fingerprint-based smart medical emergency first aid kit using IoT

1. Introduction

2. IoT in healthcare

3. Literature review

4. Proposed methodology

5. Hardware description

6. Results and discussion

7. Conclusion

8. Future enhancement

Chapter 16. An overview of the dynamics of telemedicine and robotics for the benefit of mankind

1. Introduction

2. Telemedicine and robotics as the key for a smarter future

3. Global scenario of demand and cost

4. Future aspects

5. Summary

Chapter 17. A guidance system to read and analyze the traffic rules for the visually impaired human

1. Introduction

2. The magnitude of the problem

3. Literature survey

4. Materials and methods

5. Implementation

6. Results and discussion

7. Conclusion and future work

Chapter 18. An overview of the various medical devices for diagnosis, monitoring, and treatment of diseases

1. Introduction

2. Medical devices for diagnosis

3. Monitoring of different diseases with medical devices

4. Treatment of different diseases with medical devices

5. Conclusions

Chapter 19. Efficient wireless power transfer system for biomedical applications

1. Introduction

2. Design of WPT system

3. Power conditioning units

4. Challenges and solutions

5. Conclusion

Chapter 20. Impact of IoT in biomedical applications: Part I

1. Introduction

2. Architectural levels of IoT

3. IoT sensors used in healthcare and biomedical sciences

4. IoT-based medical devices

5. Impact of IoT in healthcare

6. Security and privacy concerns in IoT-based medical devices for biomedical applications

7. Conclusion and future scope

Chapter 21. Impact of IoT in biomedical applications: Part II

1. Introduction to IoT in biomedical applications

2. Hospital management system and mobile applications using IoT

3. Integrated devices for a single parameter

4. Integrated devices for multiple parameters

5. Challenges of IoT

6. Conclusion and future work

Chapter 22. Health monitoring system

1. Introduction

2. Nanotechnology for disease diagnosis

3. Analysis of exhaled breath

4. Types of sensors

5. Smart health monitoring systems

6. Conclusion

Abbreviations

Chapter 23. Real-time remote health monitoring using IoT sensors

1. Introduction

2. IoT medical devices for health monitoring

3. Technologies integrated with IoT and blockchain for healthcare

4. Applications of IoT sensors in health monitoring

5. IoT in biomedical applications

6. Open research challenges of IoT in health monitoring

7. Conclusion

Chapter 24. E-health monitoring system

1. Introduction

2. Technology used

3. Proposed model

4. Results and discussion

5. Conclusion

Chapter 25. Comparative analysis of various supervised machine learning techniques for diagnosis of COVID-19

1. Introduction

2. Problem formulation

3. ML

4. Result analysis

5. Conclusion and future work

Index

Copyright

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Contributors

J. Ajayan,     SNS College of Technology, Coimbatore, Tamil Nadu, India

S.S. Ashraf,     School of Engineering Sciences and Technology, Jamia Hamdard, New Delhi, India

Neeta Awasthy,     GLB Group of Institutions, Noida, UP, India

Sandip Bag,     Department of Biomedical Engineering, JIS College of Engineering, Kalyani, West Bengal, India

S. Baskaran,     S.K.P Engineering College, Tiruvannamalai, Tamil Nadu, India

Soumyadeepa Bhaumik,     Heritage Institute of Technology, India

Shilpi Birla,     Manipal University, Jaipur, Rajasthan, India

Preethika Immaculate Britto,     Department of Biomedical Engineering, College of Engineering (Woman), King Faisal University, Saudi Arabia

Avik Chakraborty,     ECE Department, Jalpaiguri Government Engineering College, Jalpaiguri, West Bengal, India

Joy Chowdhury,     ECE Department, NIT, Rourkela, Odisha, India

J.K. Das,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Sourav Das,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Ananya Dastidar,     Department of Instrumentation and Electronics Engineering, College of Engineering and Technology, Bhubaneswar, Odisha, India

Ningthoujam Dinita Devi,     Radiation Oncology and Radiotherapy, RIMS, Imphal, Manipur, India

Pijush Dutta,     Department of Electronics and Communication Engineering, Global Institute of Management and Technology, Krishnagar, West Bengal, India

Souvik Ganguli,     Department of Electrical and Instrumentation Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

Karabi Ganguly,     Department of Biomedical Engineering, JIS College of Engineering, Kalyani, West Bengal, India

Anil Kumar Gautam,     Electronics and Communication Engineering, Department of North Eastern Regional Institute of Science and Technology Deemed to be University, Nirjuli, Arunachal Pradesh, India

Pratik Ghosh,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Vishnuvardhanan Govindaraj,     Department of Biomedical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu

Saumyadip Hazra,     Department of Electrical and Instrumentation Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

Satyaranjan Jena,     School of Electrical Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Harsimran Jit Kaur,     Chitkara University Institute of Engineering and Technology, Chitkara University, Punjab, India

Kakarla Hari Kishore,     Department of Electronics and Communication Engineering, Koneru Lakshmaiah Education Foundation, Guntur, India

P. Rama Krishna

Department of Electronics and Communication Engineering, Koneru Lakshmaiah Education Foundation, Guntur, India

Anurag Group of Institutions, Hyderabad, India

Rajasree G. Krishnan,     Department of Chemistry, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India

Kanak Kumar,     Electronics Engineering, IIT(BHU), Varanasi, Uttar Pradesh, India

Abhimanyu Kumar,     Department of Electrical and Instrumentation Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

Asok Kumar,     Student Welfare Department, Vidyasagar University, Medinipur, West Bengal, India

Raushan Kumar,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Rajesh Kumbhakar,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Suman Lata Tripathi,     Lovely Professional University, Phagwara, Punjab, India

Swanirbhar Majumder,     Information Technology, Tripura University, Agartala, Tripura, India

A. Mohanbabu,     Karpagam College of Engineering, Coimbatore, Tamil Nadu, India

Sushanta Kumar Mohapatra,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Pallikonda Rajasekaran Murugan,     Department of Electronics and Communication Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu

V. Nikhila,     University of Waterloo, Waterloo, Ontario, Canada

Damodar Panigrahy,     Department of Electronics and Communication Engineering, SRM Institute of Science & Technology, Kattankulathur, Tamil Nadu, India

Monika Parmar,     Chitkara School of Engineering and Technology, Chitkara University, Himachal Pradesh, India

Rajesh Kumar Patjoshi,     NIST, Berhampur, Odisha, India

P.K. Patra,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Shobhandeb Paul,     Department of Electronics and Communication Engineering, Guru Nanak Institute of Technology, Panihati, West Bengal, India

T. Poongodi,     School of Computing Science and Engineering, Galgotias University, Greater Noida, Uttar Pradesh, India

S. Prithi,     Department of Computer Science and Engineering, Rajalakshmi Engineering College, Chennai, Tamil Nadu, India

G. Boopathi Raja,     Department of Electronics and Communication Engineering, Velalar College of Engineering and Technology, Erode, Tamil Nadu, India

Shasanka Sekhar Rout,     GIET University, Gunupur, Odisha, India

Nirmal Kumar Rout,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Pradeep Kumar Sahu,     School of Electrical Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Sakthivel Sankaran,     Department of Biomedical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu

A. Santhy,     Department of Chemistry, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India

Beena Saraswathyamma,     Department of Chemistry, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India

M. Saravanan,     SNS College of Technology, Coimbatore, Tamil Nadu, India

Arghyadeep Sarkar,     Department of Electrical and Computer Engineering at McMaster University, Canada

Angsuman Sarkar,     ECE Department, Kalyani Government Engineering College, Kalyani, West Bengal, India

Shubham Saxena,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Tripurari Sharan,     Electronics and Communication Engineering, Department of North Eastern Regional Institute of Science and Technology Deemed to be University, Nirjuli, Arunachal Pradesh, India

Aanchal Sharma,     Bundelkhand Institute of Engineering and Technology, Jhansi, Uttar Pradesh, India

N.K. Shukla,     King Khalid University, Saudi Arabia

Swati Sikdar,     Department of Biomedical Engineering, JIS College of Engineering, Kalyani, West Bengal, India

Sinam Ajitkumar Singh,     Information Technology, Tripura University, Agartala, Tripura, India

Tejender Singh,     School of Electronics and Electrical Engineering, Lovely Professional University, Punjab, India

Neha Singh,     Manipal University, Jaipur, Rajasthan, India

Sinam Ashinikumar Singh,     Electronics & Communication Engineering Department, NERIST, Nirjuli, Arunachal Pradesh, India

Nagavarapu Sowmya,     GIET University, Gunupur, Odisha, India

Tanya Srivastava,     Department of Computer Science and Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

Yashonidhi Srivastava,     Department of Electrical and Instrumentation Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

D. Sumathi,     SCOPE, VIT-AP University, Amaravati, Andhra Pradesh, India

P. Suresh,     School of Mechanical Engineering, Galgotias University, Greater Noida, Uttar Pradesh, India

M. Swathi

Department of Electronics and Communication Engineering, Vignana Bharathi Institute of Technology, Hyderabad, India

CMR Institute of Technology, Hyderabad, Telangana, India

Arunprasath Thiyagarajan,     Department of Biomedical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu

Suman Lata Tripathi,     Lovely Professional University, Phagwara, Punjab, India

Sahil Virk,     Mentor Graphics Pvt. Ltd., Uttar Pradesh, India

Rohit Yadav,     School of Electronics Engineering, KIIT, Deemed to be University, Bhubaneswar, Odisha, India

Preface

Changing environmental conditions and the increase in diseases have affected human life to a large extent. In this context, researchers and industry people are continuously working to improve the performance of biomedical devices at a different level. Electronic devices and circuits are now an integral part of health diagnosis and monitoring systems. Also, the increasing demand for portable devices and wearables for health monitoring leads to the demand for ultra-low-power, efficient devices. Low power consumption led to several design challenges at the integrated circuit (IC) level with variations in device structure, material, and connectivity with other supporting biomedical equipment. The present book will cover every aspect of the biomedical device and circuit challenges to improve their performance in terms of power consumption, frequency, noise immunity, and IC area, etc. The book will also explore the new technologies and materials embedded with this biomedical equipment.

This book will help in the design and development of new low-power, high-speed, efficient biomedical devices, circuits, and systems with new technologic solutions. It will develop an understanding of new materials to improve device performance even with smaller dimensions and lower costs. This book also deals with the new methodologies to enhance system performance and will provide key parameters to explore the devices and circuit performance based on biomedical applications. The most important thing is to bridge the gap between researchers working on different areas of biomedical devices, circuits, and systems along with artificial intelligence techniques and machine learning methodologies, leading to the new technologic solutions to healthcare applications.

The impact of this title is to provide a major area of concern to develop a foundation for the implementation process and technologic solutions for new biomedical devices, circuits, and architectures. It will be helpful for researchers and designers to find out key parameters for future work in this area. The researchers working on biomedical devices and circuits can correlate their work with other requirements of smart, efficient healthcare applications.

Key features:

• The book presents the major design challenges and research potential in biomedical systems.

• The book relates healthcare system design, industries working on low-power, efficient, and highly secured biomedical electronic devices, circuits, and systems.

• The writing style of the book is simple and can be used by graduate students to PhD scholars and researchers.

• The book presents the fundamentals concepts of design and implementations in an interactive way using images and photographs for easy and fast understanding.

• There is a slow and smooth transition of the book from the basic concepts to the advanced biomedical systems designs.

• The book not only focuses on the basics but also provides real-time system designs.

• It will be helpful for researchers and designers to find out key parameters for their future work in the area of biomedical instrumentation.

Chapter organization

This book is organized into 25 chapters.

Chapter 1 gives forecasts for the reader to enlighten the upcoming research in electrochemical sensing of pharmaceuticals by exploring the properties of various carbon-based electrodes.

Chapter 2 deals with selenium-based amorphous semiconductors properties and their application in the biomedical field.

Chapter 3 deals with memories for implantable devices using nanodevices that can be used in biomedical applications where images are captured and analyzed for diagnostic and therapeutic purposes.

Chapter 4 presents the analytical model of a gate-engineered dielectric modulated junctionless nanowire transistor to efficiently detect biomolecules electrically and in a label-free manner.

Chapter 5 discusses the needs, investigation, and importance of GaN biosensors for the early diagnosis of a wide variety of diseases to provide significant reductions in death rates as a result of timely treatment, which is a present-day challenge in many developed countries.

Chapter 6 focuses on the role of electrocardiogram signal for patient monitoring systems, associated artifacts, and filtering techniques to remove these artifacts.

Chapter 7 describes the various applications regarding the importance of the prediction of sleep stage scoring based on the qualitative method along with traditional quantitative methods.

Chapter 8 emphasizes tracking of the device data, patient health using wireless remote sensing techniques, along with an ensemble of various blocks like an operational amplifier and operational transconductance amplifier.

Chapter 9 gives an idea about different types of sensor elements, used to detect events, that give data to other electronic devices, specifically for biomedical applications.

Chapter 10 gives a brief introduction to different analog-to-digital converter (ADC) and digital-to-analog converter architectures and parameters with an application for the biomedical field.

Chapter 11 introduces a reconfigurable pipeline ADC deliberated for implantable surveillance devices for bioimpedance applications.

Chapter 12 proposes a low-power successive approximation register-analog to digital converter (SAR-ADC) with a high sampling rate and implementation on 45-nm CMOS technology node for biomedical applications.

Chapter 13 presents an ultra-low-power folded cascode bulk-driven voltage to current converter, also called an operational transconductance amplifier, operating in weak inversion or subthreshold region.

Chapter 14 describes the design and comparison of electronic filters for the analysis of medical images from EEG, EMG, mammography, etc.

Chapter 15 is a fingerprint-based system that can entirely replace the usual paper-based records and electronic records system by providing recorded patient medical information such as body temperature, respiratory rate, glucose level, and heart rate.

Chapter 16 explains the transformation in the healthcare system with telemedicine and robotics technologies that provides a complementary and synergistic approach in maintaining a healthy lifestyle.

Chapter 17 focuses on aiding people to recognize traffic signals and maneuver around without help using LabVIEW.

Chapter 18 deals with the use of artificial intelligence, the internet of things (IoT), app-based detection, and monitoring techniques in the biomedical field.

Chapter 19 proposes a transmitter and receiver circuit for the wireless power transfer system to develop an optimal inductive link for implantable devices.

Chapter 20 focuses on the rising patterns of IoT-based applications that are being utilized to improve an individual's life and update their physical conditions for a healthier lifestyle.

Chapter 21 discusses patient monitoring by GPS smart soles, depression monitoring by smartwatches, glucose monitoring, efficient drug management, and hand hygiene monitoring as some of the applications of IoT.

Chapter 22 deals with the smart sensor, the system for diagnosis of diseases, precisely chronological at an early stage, and helpful to process the electromagnetic or acoustic signals.

Chapter 23 describes the overall framework of the IoT and the hindrances and challenges faced by implementing IoT in health monitoring.

Chapter 24 emphasizes on improving the current standing position of the IoT in biomedical applications.

Chapter 25 gives the proposed problem formulation containing the risk factor for COVID-19 and preceding datasets and also describes the machine learning technique for the data analysis.

Chapter 1: Carbon-based electrodes as a scaffold for the electrochemical sensing of pharmaceuticals

a special case of immunosuppressant drugs

A. Santhy, Beena Saraswathyamma, and Rajasree G. Krishnan     Department of Chemistry, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India

Abstract

This chapter envisioned the importance of carbon-based electrodes in the electrochemical sensing of pharmaceuticals, particularly immunosuppressive drugs. The scope of analytical detection of immunosuppressant drugs has expanded in recent years due to the relevance of these drugs in treatments related to organ transplantations and autoimmune diseases. In addition to the benefits, several side effects are also reported in patients with the usage of these drugs. Hence the detection of these drugs from biologic fluids and pharmaceutical dosages is highly commendable. Electrochemical methods have distinct advantages over other analytical techniques regarding simple instrumentation, fast response time, and high sensitivity. A plethora of electrochemical sensors have been fabricated for biomolecules and pharmaceuticals on carbon-based electrodes especially due to their cost-effective nature and fair electron transfer kinetics. This chapter give insights on the different carbon-based electrode materials adopted for the quantification of the immunosuppressant drugs from real samples using electrochemical methods. An overview on the analytical characteristics and the advantages of the various modified carbon electrodes in the electrochemical detection of immunosuppressant drugs is highlighted in the chapter. This forecasts the readers to enlighten the upcoming research in electrochemical sensing of pharmaceuticals by exploring the properties of various carbon-based electrodes.

Keywords

Carbon electrodes; Electrochemical sensors; Immunosuppressant drugs; Pharmaceuticals; Voltammetry

1. Introduction

A myriad of electrochemical sensors has been developed so far by various researchers for analytical applications in biologic, food, and pharmaceutical fields [1–3]. Even if many analytical techniques including chromatography, spectrophotometry, etc., [4,5] have been developed in these fields, the electrochemical techniques have garnered tremendous applications, as they gives a simple avenue for the sensitive determination of electroactive analytes with low cost [114,115]. The outstanding features of electrochemical techniques like simple instrumentation, fast response time, high sensitivity, and ease of miniaturization enthused the researchers to explore this area of research to a wide extent [6–8]. Here the review focuses on updating the advancements of electrochemical sensors in the pharmaceutical fields using carbon-based electrodes by considering immunosuppressant drugs.

Immunosuppressive drugs added a new cost-effective way of treatment to reduce the risk of graft rejection after organ transplantations [9], which flagged the development of highly sensitive analytical methods for their determinations. As the importance of immunosuppressive drugs in the healthcare system is increasing in the present scenario, it is imperative to have a quantitative and qualitative assay of these class of drugs. The researchers have been focused on acquainting copious electrochemical sensors based on new strategies for the detection of immunosuppressive drugs in recent years. Here, we highlight the characteristics of carbon-related electrochemical sensors for the analytical exploration of immunosuppressant drugs from pharmaceutical and biologic samples. The most widely used carbon-based electrodes in the electroanalytical techniques are glassy carbon electrodes (GCE), pencil graphite electrodes (PGE), carbon paste electrodes (CPE), boron doped diamond electrodes (BDDE), edge plane pyrolytic graphite electrode (EPGE), and carbon-based screen-printed electrodes (SPE). Apart from this, numerous modified carbon electrodes were also ascertained for the improved electrochemical detection of pharmaceuticals compared to bare electrodes.

2. Carbon materials used for electrode modifications

Carbon nanoparticles are extensively utilized for the modification of the electrode surface, as these possess exceptional properties due to the high surface-to-volume ratio [10,11]. The widespread use of carbon-based nanomaterials in the electrode modification process is due to the formation of a layered structure with the strong sp² carbon bonds on the surface of the transducer. This property of carbon-based nanomaterials explains its least electrical resistance and the ability to form the charge transfer complexes with the electron donating functional groups [12,13]. Carbon nanotubes (CNTs), both single walled and multiwalled, were extensively used for modifying electrodes in the electroanalytical techniques after their first invention by Sumio Iijima [14]. The high electrical conductivity, exceptional electrocatalytic activity, and superior biocompatibility make CNTs a hot subject in the modification process for the development of novel electrochemical sensors [15]. The graphene is also a propitious candidate in the fabrication of modified electrodes for various electrochemical sensing applications [16]. Graphene, a two-dimensional nanomaterial of carbon was highly exploited in the construction of electrochemical sensors for biomolecules and pharmaceuticals due to its exceptional and unique properties like high thermal conductivity, fast electron transport, and flexibility in the mechanical properties [17–19]. Reduced graphene oxides also have been altering the electrode surface in the frontiers of electrochemical sensing due to colossal surface area, electrocatalytic activity, and exquisite electrical conductivity [20–23, 111–113 ]. Nanodiamond, another carbon material entirely different in properties from large diamonds, is an emerging and attractive material in the electrochemical sensing research. Its higher conductivity due to the delocalized π bonds and its ability to form stable dispersions in aqueous media makes it attractive for exploit in the field of electrochemical sensors for pharmaceuticals [24].

Fullerene (C60), is another fascinating carbon material amply used for electrocatalytic and sensor applications [25]. The electrochemistry of fullerenes is a widely studied topic in electrochemical research. Electrochemical sensors exploring the properties of fullerenes have already been reported in various pharmaceutical applications [26,27].

3. The electroactive immunosuppressant drugs

Some of the immunosuppressant drugs have been broadly explored in the area of electrochemical sensing, and the studies related to their electrochemical detection is currently expanding. The following section gives a brief discussion on some of the drugs that have been used as the target analytes for the electrochemical studies using carbon-based electrodes. Fig. 1.1 displays some of the immunosuppressants that have been used for electroanalytical studies based on carbon-based electrodes. Tables 1.1–1.3 display the electrochemical techniques used for the detection of various immunosuppressant drugs employing carbon-based electrodes.

4. Bare carbon electrodes as a platform for the electroanalysis of immunosuppressant drugs

Mycophenolate mofetil (MPM) is a widely acknowledged immunosuppressive agent and an anticancer drug [28,29]. It is used to mitigate the risk of rejection of foreign bodies accompanying various organ transplantations in the human body [30–34]. However, miscarriage and defective fetal developments were also reported for the use of MPM by pregnant women [29]. An electrochemical sensor for MPM on unmodified GCE was reported by S N Prashanth et al. [35]. The sensor was used for the detection of MPM from urine, plasma, and tablet samples using differential pulse voltammetric (DPV) technique. A reasonable selectivity was achieved for the electrochemical detection of MPM with a wide linear range of concentration from 0.5 to 750   μM. The proposed work came to be the first reported sensor to study the electrochemical oxidation parameters of MPM. PGE has also been widely utilized in the electrochemical sensing platform for pharmaceuticals and biomolecules [8]. Recently a disposable electrochemical sensor was reported for selective determination of MPM with unmodified PGE [36]. The morphologic characterization of the PGE was done by field emission scanning electron microscopy (FE-SEM) and X-ray diffraction methods. Even without any modification, the sensor could achieve a low-level detection of MPM with an extensive concentration range of 20–1000   nM using DPV technique under optimized conditions. The selective assay of MPM from the complex matrix such as urine and pharmaceutical tablets was accomplished with acceptable recovery. The development of the highly stable disposable sensor for MPM with easy fabrication procedure could be taken as an advantage of this work over all other reported sensors.

Figure 1.1 Some of the immunosuppressant drugs used for electrochemical studies via carbon-based electrodes.

Methotrexate MTX is another drug used for the treatment of rheumatoid arthritis, chronic inflammatory diseases, and cancer treatments. Also, it is used for the treatment of severe allograft rejection associated with organ transplantations in the body [37]. The utility of an unmodified BDDE electrode in the DPV sensing of MTX from pharmaceutical and biologic samples was presented in a work [38]. The sensor exhibited a linear range of 0.05–20   μM with a relative standard deviation of 4%. Three types of pharmaceuticals samples and spiked urine were used as real samples for the detection of MTX with suitable selectivity. Ease of fabrication and sensing of MTX in low concentration range are the prominent features of this sensor in comparison to other reported works for electrochemical determination of MTX. Another drug, rapamycin (RPM), possess a dual role in the clinical fields as an anticancer drug and immunosuppressive agent [39]. From the literature survey, it seems that only two electrochemical sensors were reported for the detection of RPM. The first report was based on BDDE [40], without any modifications, and the sensor exhibited a linear range from 0.5 to 19.5   μM for the electrooxidation of RPM. The productive application of the highly selective electrode was done in biologic samples with significant recovery. Cyclophosphamide (CYP) is an important drug with immunosuppressive actions as well as having antineoplastic properties [41]. The electroreduction of CYP was studied on a GCE by Priyanka Sinha and her coworkers [42]. In differential pulse cathodic adsorptive voltammetric method (DPCAdSV), the cathodic current increased linearly as the concentration of CYP changed from 1.1 to 3.67   μM. The evaluation of the analytical pursuance of the sensing device was done by the monitoring of CYP from diluted urine samples. The application of EPGE and basal plane pyrolytic graphite electrode (BPGE) in the pharmaceutical sensing was outlined in the work for the electrochemical detection of a glucocorticoid immunosuppressant drug, hydrocortisone (HC) [43]. The roles of EPGE and BPGE in electroanalysis of various analytes were also reported in a review [44]. A nanoscale detection of HC was obtained for both EPGE and BPGE with dynamic ranges of 100–2000   nM and 500–10,000   nM respectively using Osteryoung square wave voltammetry (SWV). The feasibility of the propounded sensor was scrutinized by the quantification of HC from blood plasma and pharmaceutical samples with very low relative error. Table 1.1 displays the electrochemical sensors for the immunosuppressants via bare carbon electrodes.

5. Electroanalysis of immunosuppressants on modified carbon electrodes

Table 1.2 shows the various electrochemical sensors for immunosuppressants using modified carbon electrodes. Fig. 1.2 shows the overall representation of the electrochemical sensors for immunosuppressants based on modified carbon electrodes. GCE modified with CNTs and a magnetic nano composite was used for the electrocatalytic determination of MPM by M B Gholivand and M Solgi [45]. The multiwalled carbon nanotubes (MWCNTs) functionalized with carboxylic acid (f-MWCNT/GCE) were used for the modification of GCE, and the obtained electrode was further modified with magnetic Fe3O4 nano composite. The resulting electrode was utilized for the electrochemical detection of MPM from real samples such as urine and serum with good recovery. Differential pulse anodic stripping voltammetry (DPASV) was employed for the analytical determination under the optimized conditions, and a concentration range of 0.05–200   μM was obtained. The synergistic effect of f-MWCNT and Fe3O4 nano composite showed an excellent electrocatalytic activity toward the electrochemical determination of MPM compared to bare GCE as reported in Ref. [46] for the electrochemical detection of H2O2 using DPASV. The increase in the active surface area, the complexation of MMF with the Fe²+ ion in the Fe3O4 nanoparticle, and the higher conductivity after modification were explained to be the cause of enhanced electrochemical oxidation of MPM using this method. Also, the interaction of Fe²+ ion with the MPM was experimentally proved by spectroscopic characterization techniques in the solid state and in polar aqueous solvents [47]. The investigated method showed stability, repeatability, and selectivity for the detection of MPM from the complex matrix of the real samples.

Table 1.1

Table 1.2

Figure 1.2 Schematic illustration of electrochemical sensing of immunosuppressants using modified carbon electrodes.

The utilization of GCE modified with MWCNTs for the synchronous estimation of MPM and mycophenolic acid was described in another study by T Madrakian et al. [48]. The results of DPV showed that the modification of MWCNTs with the GCE could enhance the oxidation peak current compared to bare GCE in an analytically useful way. The sensor offered good stability and reproducibility with a working concentration range of 5–160   μM. The method enabled the selective detection of MPM from the real samples such as urine and plasma. The results displayed that the use of functionalized MWCNTs as reported in the previous work showed a 100-fold decrease in the lowest working concentration of MPM compared to unmodified MWCNTs on GCE.

Electrochemically reduced graphene oxide (ERGO) on GCE was also employed for the electrochemical detection of MPM in another work done by P S Narayana et al. [49]. A green method was adopted for the reduction of graphene oxide electrochemically on GCE. The generation of increased surface area and formation of thin films after the ERGO modification could explain the enhanced oxidation current for the MMF compared to unmodified GCE using DPV. The result showed that anodic peak current was proportional to the MPM concentration with a linear range of 40   nM–15 μM. The method has been fruitfully applied for the analytical determination of MPM from the pharmaceutical formulations with high stability and reproducibility. The ERGO-modified GCE has been applied for the selective determination of MPM in the presence of other analytes, which proved the analytical application of graphene oxide in electrochemical sensing of MPM. The results indicated that the incorporation of reduced graphene oxide on GCE for modification enabled the quantification of MPM in a lower concentration range compared with the other GCE-based sensors.

Various strategies were adopted by researchers for the electrochemical sensing of MPM using CPE. CNTs, nanoparticles of metal oxides, ionic liquids, etc., were employed to modify CPEs in various studies. A voltammetric sensor for simultaneous detection of MPM with tryptophan was described in the study of Mohsen Ashjari and his coworkers [50]. A three-step modification process was done on CPE with carboxylated single-walled carbon nanotubes (SWCNTs), magnesium oxide nanoparticle, and a room temperature ionic liquid, n-hexyl-3-methylimidazolium hexafluoro phosphate. The sensor exhibited excellent sensitivity for the electrochemical detection of MPM with a linear range of 0.1–450   μM. The rate of electron transfer was highly improved after the modification due to the large surface area and low charge transfer resistance. Hence a better oxidation peak current for MPM in presence of tryptophan was observed for the modified electrode compared to the bare CPE. SWV was utilized to study the electrochemical characteristics of MPM under the optimized parameters. The electrode was implemented for the detection of MPM from pharmaceutical dosage forms and serum successfully and proven to be a selective sensor for MPM. The combination of SWCNT-MgO nanocomposite and room temperature ionic liquids on CPE was also reported for the successful electrochemical detection of vanillin and tramadol [51,52].

In another study by Firuzeh Hosseini et al. [53], a combination of NiO/SWCNTs and 1-methyl-3-butylimidazolium bromide was used for the modification of CPE. The modified electrode possessed a large surface area and acts as good conducting substrate for the electrooxidation of MPM when compared to bare CPE. These characteristics enabled the sensor to achieve a higher anodic peak current for the electrochemical oxidation of MPM with a wide linear range of 0.08–900   μM. The real-time application of the device was done by the electrochemical detection of MPM in pharmaceutical serum and tablet samples using SWV. From the results obtained, the sensor displayed a concentration range that is better than that reported by Mohsen Ashjari et al. [50].

Molecular imprinted polymers (MIPs) are found to be a highly promising candidate for the electrochemical sensing platform due to their outstanding selectivity toward a target molecule. MIPs are synthetic polymers formed by the polymerization of certain monomers in the presence of target analytes as the template molecule. The template molecule is further removed selectively from the polymer matrix by extraction with suitable solvents. The resulting thin polymer film on the electrode carries some cavities that suit the shape and size of the analyte molecules. The electrochemical response obtained when this thin polymer encounters the solution containing the analyte molecules is responsible for the electrochemical sensing of the analyte [54]. The general procedure for the MIP sensors is illustrated in Fig. 1.3. A MIP sensor based on CPE for the electrochemical detection of MMF has been developed by H Momeneh and M B Gholivand [55]. The MIP was prepared from the methacrylic acid as the monomer with MPM as the template molecule. The MIPs in combination with MWCNTs were used to modify the CPE, which improved the conductivity of the sensor. With the optimized analytical parameters, SWV was employed for the analytical determination of MPM from the real samples such as serum and urine with high accuracy and precision. The sensor exhibited good selectivity and repeatability, and a dynamic concentration range of 9.9   nM–87   μM was obtained from the calibration plot for the electrooxidation of MPM.

Figure 1.3 Schematic representation of procedures involved in MIP-based electrochemical sensors.

The construction and optimization of the electrochemical sensor for MPM along with another immunosuppressant drug tacrolimus was reported by M H Mahnashi et al. on pencil graphite electrode [56]. Tacrolimus pertains to the class of calcineurin inhibitors and is used for patients having organ transplantation to avoid the rejection of graft. This was the first attempt done by the researchers to fabricate an electrochemical sensor for the simultaneous detection of MPM with another drug. The sensor utilizes electropolymerization technique to modify the PGE with MWCNT and a metal organic framework (MOF) Cu–1N-allyl-2-(2,5-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (Cu-ADPPI MOF) to obtain a disposable electrode for the quantification of MPM and tacrolimus together. MOFs are found to be a good choice of material for the modification of carbon-based electrodes in electrochemical sensing research due to their excellent host–guest interactions with the analyte molecules [57]. The MOFs are associated with internal cavities containing multiple pores with various sizes and shapes, which are attributed to their sensing properties. Using DPV technique, they reported a highly stable and reproducible sensor for MPM and tacrolimus with a dynamic concentration range of 0.85–155 × 10 −⁸   M and 1.1–170.0 × 10 −⁸   M respectively. The result was found to be the lowest concentration range ever reported for electrochemical sensing of MPM. The sensor was highly selective in nature and was analytically applied for the analysis of MPM from biologic fluids such as urine and plasma with fair recovery.

Azathioprine (AZA) is an immunosuppressant drug having a clinical history of around 25 years. This drug is used to treat acute inflammatory disease and reduce the risk of graft rejection in the posttransplantation stage [58]. Nanodiamond, a novel carbon material, was introduced as modifier in a work for the electrochemical detection of AZA with a linear range of 0.2–100   μM [59]. Chitosan (CS) is added as a dispersive agent for the nanodiamond, and electroreduction of AZA could be achieved on the modified GCE with the cathodic current approximately 70 times higher than that of bare GCE using CV technique. The practical employability of the sensor was done from the pharmaceutical tablets and blood serum. A gold neuronal-like nanostructure was synthesized by wet chemical method by Mei L. P. et al. [60] and was used to decorate GCE for the electrochemical detection of AZA. A linear range of 0.5–2300   μM was obtained using DPV and was analytically applied in the blood serum samples. A cyclic voltammetric determination of AZA was reported in another work [61] using carbon nanoparticle (CNP)-modified GCE with a linearity of 0.2–50   μM. The CNPs were drop casted on the Nafion-coated GCE, and an enhancement of reduction peak current of about 40 times to that of bare GCE was obtained.

A pyrolytic graphite electrode was employed by Elham Asadian et al. for the SWV determination of AZA from real samples such as azathioprine tablets and blood serum [62]. Graphene nanosheets modified with Ag nanoparticles were decorated on pyrolytic graphite electrode to detect AZA electrochemically over a linear range of 0.7–100   μM. The metal nanoparticle-modified graphene nanosheets were an excellent material in the electrochemical sensing application due to the combined effect of graphene and metal nanoparticles [63]. Moreover, a highly reproducible and stable electrochemical sensor for AZA was delineated in another report [64] by the electrodeposition of graphene-CS nanocomposite on GCE with high electrical conductivity. Using SWV a linear concentration of range 0.1–26   μM was achieved, and the real sample application was done on tablets and blood serum. MWCNTs are utilized for the selective and sensitive determination of AZA on GCE substrate [65]. A composite film of manganese oxide microcube-modified MWCNTs on GCE provided a concentration range 0.045–2530   μM of AZA by amperometric determination. This broad working concentration range of AZA like that reported in Ref. [60] is one of the highlights of this sensor when compared to all other electrochemical sensors for AZA mentioned in this review.

The technology of developing disposable SPE using carbon-based ink was beneficially applied in electrochemical sensing applications due to low cost and wide potential window with minimum background currents [66]. An MWCNT-modified SPE was introduced for the SWV determination of MTX in the pure and dosage form by Shi Wang et al. [67]. A linear range of MTX concentrations was obtained from 0.5 to 100   μM. Cetyltrimethylammonium bromide CTAB solution was used for dispersing the MWCNTs on SPE. The screen printing by inkjet technology was considered a more efficient method for modifying electrodes than the conventional drop casting methods [68]. A nondisposable electrochemical sensor for MTX was portrayed through a functionalized MWCNT carbon paste electrode in another report [69]. Both DPV and SWV were used to measure the electrochemical response of MTX with linear concentration ranges of 0.4–5.5   μM and 0.01–1.5   μM respectively. Using standard addition method, electrochemical quantification of MTX from undiluted synthetic urine, blood serum, and pharmaceutical tablets by DPV technique was achieved. Thus, the sensor was successfully utilized for the in vitro analysis of real samples with high selectivity in the complex matrix and could be taken as a benefit of this work over other electrochemical sensors for MTX.

In another report [70], the simultaneous determination of MTX and doxorubicin, an antineoplastic drug, was described on a cyclodextrin-graphene hybrid nanosheet-modified glassy carbon electrode (CD-GNs/GCE). The obtained electrochemical response was about 23.7 times higher than that of unmodified GCE. The sensor showed a linear range of 0.1–1   μM using DPV measurements. Besides, the CD-GNs/GCE possessed high selectivity and stability for the electrochemical detection of MTX and certainly is considered an analytical tool for the determination of MTX from real samples.

Graphite oxide or graphitic acid is a pseudo-two-dimensional carbon-based material, and electrochemical sensors based on this are reported for the drug acetaminophen [71]. The fabrication of a graphite oxide-Nafion-coated GCE and the CV response of MTX on this electrode were presented in a work [72] with a linear range of 0.4–20   μM. The interference study was also conducted, and the analysis of MTX in methotrexate injection and urine was done. The suggested sensor was found to be reliable for the determination of MTX from real samples as results were compared with standard reference method.

Another surfactant-modified CPE decorated with CNTs was introduced for the detection of MTX using CV by Jamballi G. Manjunatha [73]. A linearity was obtained in the range of 0.2–7   μM with excellent stability and reproducibility. The adsorbing property of surfactants on the electrode surface leads to the enhancement in the electrochemical response of analytes in electrochemical sensors [74]. Three different surfactants such as sodium dodecyl sulfate (SDS), CTAB, and Triton X-100 were used for the modifications with CNT, and later, SDS-CNT CPE was used for analytical applications as the electrochemical response was better when compared to the other two electrodes. The dynamic linear range obtained by CV is 0.2–7   μM. The detection of MTX from commercially available methotrexate injection was done with reasonable accuracy.

The first concurrent detection of doxorubicin and MTX was reported on an amperometrically electrodeposited copper nanoparticle-modified Nafion-carbon black film-coated GCE [75]. The observed linear working range of MTX was 2.2–25   μM using SWV. The use of carbon black, another significant carbon nanomaterial, along with metal nanoparticles shed light on the various areas of electrochemical sensing research [76,77]. The aforementioned sensor was applied to determine the MTX concentration from human urine samples and river water samples with good recovery. Thus, the sensor works consistently in the electroanalytical detection of MTX from both biologic and environmental samples. The electrooxidation of MTX in the presence of 8   μM calcium folinate on a GCE was described in a report [78]. The sensor was prepared by electropolymerizing para amino benzene sulphonic acid (p-ABSA), a conducting polymer, on an amine functionalized MWCNT-modified GCE. The calibration plot showed a linearity from 0.1 to 8   μM for MTX concentrations in DPV measurements. The electrode was fruitfully applied for the detection MTX in presence of calcium folate from urine sample with excellent selectivity.

Self-assembled monolayers of gold nanoparticles on GCE were practically applied for MTX detection from pharmaceutical dosage forms and blood serum samples by SWV technique [79]. The sensor detects the concentration range of MTX from 0.04 to 2   μM. A very low concentration of MTX was detected by the sensor compared with bare GCE without much interference with the other species present in real sample matrices. Another reported work for the quantitative determination of MTX was based on poly L-lysine modification on GCE [80]. The electrochemical response of MTX was evaluated by CV with and without the surfactant sodium dodecyl benzene sulfonate. The enrichment in the anodic peak current was obtained for the former and was chosen for the feasible application of the sensor. In SWV experiments, the concentration range of MTX follows a linear increase from 0.005 to 0.2   μM. The highly stable and selective sensor was employed for the quantitative assay of MTX from tablets and human serum with satisfactory recovery.

A combination of CNT and graphene were presented in Ref. [81] for the modification of GCE to electrochemically quantify MTX from real samples such as tablets and human serum. The coupled effect of the three-dimensional network of CNT and graphene improved the electrochemical response of MTX on the modified electrode. Under optimized electrochemical parameters, the DPV showed a wide linear range from 0.7 to 100   μM, when compared with other reports. MTX and epirubicin, another antineoplastic drug, were simultaneously detected using an SPE modified with Au-MWCNT-ZnO nanocomposite [82]. The SWV studies showed that a linear range of 0.02–1   μM for the pure form of MTX solution. This single-use sensor was conveniently used for the investigation of MTX from commercially available injections and whole blood samples.

In another approach, CoFe2O4 nanoparticle-decorated reduced graphene oxide electrode was used for the selective determination of MTX from pharmaceutical samples with good results [83]. The properties of graphene oxide along with metal nanoparticles could enhance the electrochemical response of MTX compared to unmodified, and the oxidation current was found to be proportional to the MTX concentrations from 0.05–7.5   μM.

Surfactants have proven to be an excellent material for tailoring the electrodes in electrochemical sensors. As we discussed previously, different works were reported for the electroanalytical quantification of MTX based on various surfactants. One more electrochemical sensor for MTX based on the surfactant dihexadecylhydrogenphosphate (DHP) was fashioned on MWCNT-modified GCE [84]. The MWCNT was immobilized on the DHP film to obtain a highly repeatable electrode for the detection of MTX from tablets. The anodic peak current was increased proportionally in a range of 0.005–5   μM using differential pulse adsorptive stripping voltammetry (DPAdSV).

Molecular imprinting technology was adopted for the electroanalytical detection of CYP on GCE [85]. A nitrogen and sulfur co-doped activated graphene was drop casted on a GCE followed by the electropolymerization of o-aminophenol in the presence of CYP to get an MIP electrode. Similarly, a nonimprinted (NIP) electrode was also prepared with same procedure without CYP for comparative measurements. The CV measurements of MIP were done after leaching with 0.1   M NaOH, and a concentration range of 8 pM–0.8   μM was obtained in the calibration plot. The real-time analytical application was done on the blood serum samples collected from rabbit after a dose of CYP was administered. A good result was achieved for the electrochemical detection of CYP due to the highly conducting nature of heteroatom-doped graphene and the highly selective molecular imprinted cavities on the modified electrode toward CYP. This is the only work reported for the electrochemical detection of CYP in picomolar concentrations.

Dexamethasone (DMS), a synthetic derivative of glucocorticoid hydrocortisone, is a commonly used drug with immunosuppressive and antiinflammatory properties [86]. The electroanalytical determination of DMS utilizing the properties of C60 using GCE and pyrolytic graphite electrode was demonstrated in a report [87]. A comparative description of the two electrodes was also highlighted in the report. A solution of C60 in dichloromethane is drop coated on the GCE and pyrolytic graphite electrode followed by pretreatment and electrochemical activation of C60 film by CV technique. The resulting conductive film [88] obtained was electrochemically evaluated by SQW for the detection of DMS. The results showed that the C60-modified pyrolytic graphite electrode showed less negative reduction potential for the electroreduction of DMS with enhanced peak current compared to C60-modified GCE. The C60-modified pyrolytic graphite electrode showed a concentration range of DMS from 0.05–100   μM in the calibration plot. The real-time application of the highly stable and reproducible sensor was conducted successfully on blood plasma samples collected from patients with DMS treatments and from tablet samples.

A nanocomposite material of hematite and graphene oxide was synthesized, characterized, and was coated on a GCE to obtain an electrochemical sensor for DMS in blood plasma [89]. The combined effect of hematite nanoparticles and graphene oxide provided a high surface-to-volume ratio, which enhanced the sensitivity of the sensor compared to GCE without modification. The DPV method was investigated to study the electrooxidation of DMS and two linear concentration ranges of 0.1–10   μM and 0.1–50   μM. The sensor provided a simple method for the DMS from real samples without much interference from the coexisting species in the complex matrix. The sensitive determination of DMS from blood serum and urine samples was achieved on a copper (II)-loaded Fe3O4-polyaniline (PANI) nanocomposite-decorated ionic liquid (IL)-modified CPE [90]. The electrochemical response of bare CPE, CPE-IL, CPE-IL-Fe3O4, CPE-IL-Fe3O4-PANI, and CPE-IL-Fe3O4-PANI-CuII were investigated by CV in the presence of DMS. An improvement in the peak current for CPE-IL-Fe3O4-PANI-CuII compared to all other electrodes suggested the synergistic effect of the modifiers on the electrochemical oxidation of DMS. Under optimized conditions, the DPV studies showed a linear increase in concentration of DMS from 0.05–30   μM. A satisfactory recovery was obtained for the determination of DMS in the practical application for the highly selective and reproducible CPE-based electrochemical sensor. The use of electropolymerization technique was used to fabricate an electrochemical sensor for DMS on CPE. The electrode was developed by forming a thin film of poly-glycine on an MWCNT-modified CPE [91] The electrochemical behavior of the electrochemically tailored electrode was studied by DPV, SWV, and linear sweep voltammetry (LSV). Linear concentration ranges of 7.16–85.6   mM, 4.78–143.4   mM, and 0.19–19.2   mM were obtained for DPV, SWV, and LSV, respectively, for the electrooxidation of DMS. The recoveries of DMS from a 1:1 solution of dopamine, ascorbic acid, and uric acid were calculated using LSV. The sensor showed no significant interferences, and the simultaneous determination of dopamine and DMS was also achieved with LSV measurements. Also, the sensor was practically employed to monitor the amount of DMS from spiked urine samples with very low relative error.

Rajendra N. Goyal et al. reported the use of MWCNT on EPGE and the effect of the surfactant CTAB for the electrochemical analysis of DMS [92]. Because of the hydrophobic interaction, CTAB will form a stable film on MWCNT-modified EPGE. The MWCNT suspension was drop coated on the EPGE surface, and CV was used to analyze the electrochemical response of DMS in the presence and absence of CTAB. An amelioration in the cathodic peak current was noticed for DMS with CTAB compared to the other, suggesting the electrocatalytic activity of the CTAB along with MWCNT for the electroreduction of DMS. The concentration of the DMS varied linearly with the reduction peak current of DMS from 1   nM to 100   μM with CTAB in SWV measurements. The real-time monitoring of commercially available DMS tablets and human urine collected from the patients, who have been treated with DMS tablets, was performed with the highly reproducible sensor.

Another sensor based on graphene nanoparticle-modified GCE was reported for the selective determination of DMS from blood plasma and pharmaceutical samples [93]. For electrochemical determination of the DMS, varieties of graphene such as quantum dot of graphene, graphene oxide (GO), electrochemically synthesized graphene, reduced graphene, and graphene nanoplate (GNP) were used to tailor the properties of the GCE surface. The best result for the electrochemical reduction of DMS was achieved from GNP-modified GCE compared to other developed electrodes. Two linear ranges of 0.1–50   μM and 50–5000   μM were obtained in the calibration plot for the DPV studies of GNP-modified GCE. With the appropriate analytical conditions, the sensor was applied for the detection of DMS from real samples with reasonable stability.

The use of PGE for the square wave voltammetric determination of DMS from pharmaceutical and biologic samples was developed in another work [94]. The sensor was fabricated by modifying the PGE with activated MWCNT and was studied by CV, electrochemical impedance spectroscopy, and SEM. The effect of MWCNT increases the anodic peak current of DMS and reduces the oxidation over potential compared to bare PGE. A linear range of 0.15–100   μM was obtained for the detection of DMS. The individual determination of three immunosuppressive drugs, DMS, prednisolone (PDN), and HC, on a β-cyclodextrin (β-CD)-modified CPE was elucidated in Ref. [95]. The electroreduction of keto groups in these glucocorticoid drugs resulted in sharp peaks on the modified CPE, and the current obtained was more than that of bare CPE because of the cyclodextrin on the CPE. The cyclodextrins are familiar for the formation of inclusion complexes with the guest analytes, and this was a widely studied topic [96]. The β- CD-modified CPE was applied analytically for the determination of these drugs from serum, tablets, and urine samples by DPV. The linear ranges obtained for DMS, PDN, and HC were 0.41–20   μM, 0.56–20   μM,