The Detection of Biomarkers: Past, Present, and the Future Prospects

Description

Reliable, precise and accurate detection and analysis of biomarkers remains a significant challenge for clinical researchers. Methods for the detection of biomarkers are rather complex, requiring pre-treatment steps before analysis can take place. Moreover, comparing various biomarker assays and tracing research progress in this area systematically is a challenge for researchers. The Detection of Biomarkers presents developments in biomarker detection, including methods tools and strategies, biosensor design, materials, and applications. The book presents methods, materials and procedures that are simple, precise, sensitive, selective, fast and economical, and therefore highly practical for use in clinical research scenarios. This volume situates biomarker detection in its research context and sets out future prospects for the area. Its 20 chapters offer a comprehensive coverage of biomarkers, including progress on nanotechnology, biosensor types, synthesis, immobilization, and applications in various fields. The book also demonstrates, for students, how to synthesize and immobilize biosensors for biomarker assay. It offers researchers real alternative and innovative ways to think about the field of biomarker detection, increasing the reliability, precision and accuracy of biomarker detection. Front Cover The Detection of Biomarkers Copyright Page Contents List of contributors Preface 1 Introduction to biomarkers 1.1 Introduction 1.2 Classification of biomarkers 1.2.1 Genomic biomarkers 1.2.2 Transcriptomic biomarkers 1.2.3 Epigenomics biomarkers 1.2.4 Proteomic biomarkers 1.2.5 Metabolomic biomarkers 1.2.6 Low molecular weight biomarkers 1.3 Biomarker discovery and diagnosis techniques and strategies 1.4 Biomarker validation 1.5 Biological matrices used for detection 1.5.1 Tissue bronchoscopy 1.5.2 Exhaled breath condensate 1.5.3 Blood circulation 1.5.4 Body fluids 1.5.5 Skin 1.5.6 Hair and nails 1.6 Applications of biomarkers in medicine 1.7 Future prospects Acknowledgement References 2 Low-molecular-weight biomarkers: types and detection strategies 2.1 Introduction 2.2 Type of low-molecular-weight biomarkers 2.2.1 Reactive oxygen species 2.2.2 Reactive nitrogen species 2.2.3 Volatile organic compounds 2.2.4 Modified amino acids and their metabolites 2.2.5 Fatty acids and their metabolites 2.2.6 Modified nucleotides (DNA and RNA fragments) 2.2.7 Carbohydrate metabolites 2.2.8 Vitamin metabolites 2.2.9 Hormones 2.2.10 Electrolytes 2.3 Low-molecular-weight detection strategies 2.3.1 Immunohistochemistry-based detection strategy 2.3.2 Real-time quantitative polymerase chain reaction 2.3.3 Chromatography 2.3.4 Mass spectroscopy 2.3.5 Biosensors 2.3.5.1 Optical biosensors 2.3.5.1.1 Fluorescence-based biosensors 2.3.5.1.2 Luminescence and colorimetric 2.3.5.2 Enzyme-linked immunosorbent assay 2.3.5.3 Surface plasmon resonance 2.3.5.4 Acoustic biosensors 2.3.5.5 Electrochemical biosensors 2.3.5.5.1 Application of nanomaterials in electrochemical biosensors 2.3.5.5.2 Electrochemical biosensors with no using electron mediators 2.3.5.6 Magnetic biosensors 2.4 Bioapplications of low-molecular-weight detection 2.4.1 Diagnostic and inflammatory biomarkers 2.4.2 Prognostic biomarkers 2.4.3 Predictive biomarkers 2.5 Conclusion References 3 Circulating miRNAs as biomarkers for noninvasive cancer diagnosis 3.1 Introduction 3.2 An overview of miRNAs 3.2.1 Historical overview 3.2.2 Biogenesis of miRNAs 3.2.3 Circulating miRNAs 3.2.4 miRNAs as cancer proliferation and suppression agents 3.3 Definition of biosensors 3.4 Optical biosensors 3.5 Colorimetric biosensors 3.6 Fluorescence-based biosensors 3.7 Chemiluminescence- and electrochemiluminescent-based biosensors 3.8 Surface plasmon resonance-based biosensors 3.9 Electrochemical biosensors 3.9.1 Introduction 3.9.2 (Chrono)Amperometry 3.9.3 Cyclic voltammetry 3.9.4 Differential pulse voltammetry 3.9.5 Square wave voltammetry 3.9.6 Potentiometry 3.9.7 Conductimetry 3.9.8 Impedance 3.9.8.1 Electrochemical impedance spectroscopy 3.10 Future perspectives Acknowledgments References 4 Cardiac biomarkers: definition, detection, diagnostic use, and efficiency 4.1 Cardiac biomarkers of the acute coronary syndrome 4.1.1 Definition and history 4.1.1.1 Aspartate aminotransferase 4.1.1.2 Lactate dehydrogenase 4.1.1.3 Myoglobin 4.1.1.4 Creatine kinase 4.1.1.5 CK-MB 4.1.1.6 Cardiac troponins 4.1.2 Development of cardiac troponin assays 4.1.2.1 cTnI assays 4.1.2.2 cTnT assays 4.1.2.3 Cardiac troponins in acute coronary syndrome 4.1.2.4 Development of high sensitivity troponin assays 4.1.3 Other markers of acute coronary syndrome 4.1.3.1 Heart-type fatty acid–binding protein 4.1.3.2 Myeloperoxidase 4.2 Biomarkers of cardiac failure 4.2.1 Natriuretic peptides 4.3 Biomarkers of coronary heart disease 4.3.1 C-reactive protein 4.3.2 Homocysteine 4.4 Conclusion 4.4.1 Go to 4.4.1.1 Diagnostic tests 4.4.2 Go to 4.4.2.1 Interfering factors 4.4.3 Go to 4.4.3.1 Results, reporting, critical findings 4.4.4 Go to 4.4.4.1 Clinical significance 4.4.5 Go to 4.4.5.1 Enhancing healthcare team outcomes References 5 Proteomic-based identification of novel biomarkers 5.1 Introduction 5.2 Designing a biomarker discovery study 5.3 Methodologies for proteomic-based biomarker discovery studies 5.3.1 Mass spectrometry-based proteome profiling 5.3.1.1 Digestion of proteins 5.3.1.2 Separation methods of proteins and peptides 5.3.1.3 Microfluidic systems for sample preparation and separation 5.3.1.4 Ionization methods of proteins and peptides 5.3.1.5 Mass spectrometry instrumentation 5.3.1.6 Analysis of the tandem mass spectra 5.3.1.7 Protein quantification methods 5.3.1.8 Verification of proteomic biomarkers 5.3.1.9 Validation of proteomic biomarkers 5.3.2 Antibody-based proteomics approaches 5.3.3 Data-dependent acquisition and data-independent acquisition mass spectrometry 5.4 The current state of proteomic-based biomarkers 5.4.1 Advantages of proteomic-based biomarker discovery research: posttranslational modifications as disease biomarkers 5.4.2 Mass spectrometry imaging and profiling in biomarker discovery research 5.4.3 Detection of protein-protein interactions by proteomic-based approaches 5.5 Clinical biomarkers discovered by proteomic approaches 5.6 Limitations 5.7 Future perspectives References 6 Metabolomics tools for biomarker discovery: applications in chronic kidney disease 6.1 Introduction 6.1.1 Metabolomics 6.1.2 Biomarkers 6.1.3 Chronic kidney disease classical biomarkers 6.2 Metabolomics tools for the discovery of novel renal disease biomarkers 6.2.1 Metabolomics techniques 6.2.2 Type of studies: targeted versus untargeted 6.2.3 Workflow in metabolomics 6.2.3.1 Sample collection 6.2.3.2 Sample analysis 6.2.3.3 Data treatment 6.2.3.4 Annotation and identification of compounds 6.2.3.5 Metabolic pathway analysis 6.2.3.6 Biomarkers development: discovery, translation, and validation 6.2.4 Metabolomics studies of validated new biomarkers in chronic kidney disease 6.2.5 Metabolomics as a clinical tool in chronic kidney disease 6.2.5.1 Limitations of metabolomics tools in chronic kidney disease precision medicine 6.2.5.2 Future perspectives of metabolomics in the clinical study of chronic kidney disease References 7 Electronic devices for biomarker monitoring 7.1 Introduction 7.2 Biomarkers 7.3 Sensing electronic devices: transistors 7.3.1 Basics: charged interfaces 7.3.2 Conventional ion sensitive field-effect transistors 7.3.3 Dual-gate ion sensitive field-effect transistors 7.3.4 Nano-ISFETs 7.3.5 Electrical double-layer field-effect transistors and electrolyte-gated field-effect transistors 7.3.6 Organic electrochemical transistors 7.3.7 Extended-gate field-effect transistors 7.4 Conclusion and perspectives References 8 Novel advances in nanomaterial-based electrochemical sensing of the biomarker 8.1 Introduction 8.2 Classification of biomarkers 8.2.1 Genomics 8.2.2 Metabolomics 8.2.3 Proteomics 8.3 Various nanomaterials as signal amplification 8.4 The novel advance of immobilization strategies for biomarkers 8.4.1 Adsorption 8.4.2 Entrapment 8.4.3 Cross-linking 8.4.4 Electrostatic interactions 8.4.5 The biological affinity of biomolecule 8.5 Trends research on electrochemical nano-biosensing of the biomarkers 8.5.1 Biomedical application of electrochemical biosensors in clinical monitoring 8.6 Conclusion and future perspectives References 9 Carbon nanomaterials-based electrochemical cancer biomarkers biosensors 9.1 General concepts 9.2 Carbon nanostructures-based electrochemical (bio)sensors for the quantification of cancer biomarkers 9.2.1 microRNA 9.2.2 Prostate-specific antigen 9.2.3 Alpha-fetoprotein 9.2.4 Carcinoembryonic antigen 9.3 Conclusions and perspectives Acknowledgments References 10 Optical nanosensor based on surface-enhanced Raman spectroscopy for biomedical and biomarker detection applications 10.1 Introduction 10.2 Raman spectroscopy techniques for biomedical applications 10.3 Surface-enhanced Raman spectroscopy-based applications in biomarkers 10.3.1 Biomarkers 10.3.2 Protein biomarkers 10.3.3 Glucose 10.3.4 Nucleic acids 10.3.5 Pathogens 10.4 Surface-enhanced Raman spectroscopy applications in bioimaging 10.5 Raman activated cell sorting 10.6 Surface-enhanced Raman spectroscopy-based microchip system 10.6.1 ITO integrated SERS microfluidic chip system 10.6.2 Surface-enhanced Raman spectroscopy-based passive microchip 10.6.3 Microfluidic dielectrophoresis device 10.6.4 Dual responsive disposable electrode microchip 10.7 Surface-enhanced Raman spectroscopy mapping 10.7.1 Paper-based Surface-enhanced Raman spectroscopy mapping 10.7.2 Surface-enhanced Raman spectroscopy mapping for cancer 10.7.3 Surface-enhanced Raman spectroscopy mapping on nanocellulose membranes 10.8 Conclusions and future prospects References 11 Optical smartphone-based sensing: diagnostic of biomarkers 11.1 Introduction 11.1.1 Definition and clinical significance of biomarkers 11.1.2 Discovery and validation of clinically relevant biomarkers 11.1.3 Use of biomarkers to reach personalized medicine: from laboratory-based measurements to point-of-care technologies 11.2 Optical smartphone-based biosensors for the detection of biomarkers 11.2.1 Colorimetric point-of-care biosensors based on smartphone camera 11.2.2 Fluorescence point-of-care biosensors based on smartphone camera 11.2.3 Luminescence biosensors on smartphone camera 11.2.4 Microscopy point-of-care biosensors based on smartphone camera 11.2.5 Surface plasmon resonance point-of-care biosensors based on smartphone camera 11.3 Summary and future perspectives Acknowledgments References 12 Design of immunosensors for rapid and sensitive detection of biomarkers 12.1 Immunosensor 12.2 Biomarkers and their classification 12.3 Antibodies and their immobilization methods 12.4 Immunosensor formats 12.5 Applications of nanomaterials to amplify the analytical signal of immunosensors 12.5.1 Analytical signal strengthening using nanomaterials as substrates 12.5.2 Analytical signal strengthening using nanomaterials as carriers and labels 12.6 Transducers used for immunosensors 12.6.1 Amperometric and voltammetric immunosensors 12.6.1.1 Label-free immunosensors 12.6.1.2 Immunosensors with enzymatic labels 12.6.1.3 Immunosensors with electrochemically active labels 12.6.2 Potentiometric immunosensors 12.6.3 Surface plasmon resonance immunosensors 12.7 Multiplexed assay–based immunosensors for biomarkers detection 12.7.1 Electrochemical multiplexed assay 12.7.2 Optical multiplexed assay–based immunosensors 12.8 Conclusions and future outlook Acknowledgments References 13 Recent advances in immunosensors for healthcare 13.1 Introduction 13.1.1 Principles of an immunosensor 13.1.2 Antibodies and their application to immunosensors 13.1.2.1 General description of antibodies 13.1.2.2 Antibody immobilization techniques 13.1.2.2.1 Noncovalent immobilization 13.1.2.2.2 Covalent immobilization 13.1.2.3 Immunosensor classification format 13.1.2.3.1 Direct immunoassay 13.1.2.3.2 Indirect competitive immunoassay 13.1.2.3.3 Indirect noncompetitive immunoassay (sandwich format) 13.1.2.4 The use of labels for signal generation and amplification 13.1.2.4.1 Radioactive isotopes 13.1.2.4.2 Enzymes 13.1.2.4.3 Fluorogenic reporters 13.1.2.4.4 DNA reporters 13.1.2.4.5 Nanomaterials 13.1.2.5 Label-free immunoassays 13.1.3 Detection systems using antibodies 13.1.3.1 Optical immunosensors 13.1.3.1.1 Fluorescence detection 13.1.3.1.2 Surface plasmon resonance 13.1.3.2 Piezoelectric immunosensors 13.1.3.3 Electrochemical immunosensors 13.1.3.3.1 Amperometry 13.1.3.3.2 Electrochemical impedance spectroscopy 13.1.3.3.3 Voltammetry 13.1.3.3.4 Potentiometry 13.1.3.3.5 Photoelectrochemical immunosensors 13.1.3.3.6 Electrochemiluminescence 13.2 Immunosensors for healthcare 13.2.1 Detection of pathogens and toxins 13.2.2 Rapid detection of cancer biomarkers 13.2.3 Smart, portable, and noninvasive diagnostic immunosensors for healthcare 13.2.3.1 Lateral flow assays 13.2.3.2 Microfluidic paper-based analytical devices 13.2.3.3 Smartphone-based immunosensors 13.3 Summary and outlooks References 14 Impedimetric immunosensors for detection of biomarkers 14.1 Introduction 14.1.1 Biomarkers 14.1.2 Electrochemical impedance spectroscopy 14.1.2.1 Protein-based biomarkers 14.1.2.2 Lung cancer 14.1.2.2.1 Neuron-specific enolase 14.1.2.2.2 Carcinoembryonic antigen 14.1.2.2.3 CYFRA21-1 14.1.2.2.4 Squamous cell carcinoma antigen 14.1.2.2.5 Other 14.1.2.3 Breast cancer 14.1.2.3.1 Human epidermal growth factor receptor 2 14.1.2.3.2 Carbohydrate antigen 15-3 (CA15-3, also known MUC-1) 14.1.2.3.3 Other 14.1.2.4 Ovarian cancer 14.1.2.4.1 CA125 14.1.2.4.2 Human Epididymis Protein 4 14.1.2.4.3 Other 14.1.2.5 Prostate cancer 14.1.2.6 Cardiovascular diseases 14.1.2.7 Neurodegenerative diseases 14.1.2.8 Nucleic acid-based biomarkers 14.1.2.8.1 DNA-based biomarkers 14.1.2.8.2 DNA methylation 14.1.2.8.3 p53 14.1.2.8.4 Epidermal growth factor receptors 14.1.2.8.5 Breast cancer susceptibility gene/1 14.1.2.8.6 Other 14.1.2.8.7 RNA-based biomarkers 14.1.2.8.8 mRNA 14.1.2.8.9 miRNA 14.1.2.8.10 Tumor cell-based biomarkers 14.2 Conclusion and future remarks References 15 Conducting polymers—versatile tools in analytical systems for the determination of biomarkers and biologically active co... 15.1 Introduction 15.1.1 Chemical polymerization–based synthesis of conducting polymers 15.1.2 Living-cell and microbe-assisted synthesis of conducting polymers 15.1.3 Electrochemical formation of conducting polymer-based layers 15.1.4 Physicochemical properties of conducting polymers 15.1.5 Application of electrochromic polymers in sensor design 15.1.6 Conducting polymers–based electrochromic sensors 15.1.6.1 Polyaniline-based electrochromic sensors 15.1.6.2 Polypyrrole-based electrochromic sensors 15.1.6.3 Polythiophene-based electrochromic sensors 15.1.6.4 Proteins entrapment within polymer layers during the development of catalytic and affinity sensors 15.1.6.5 Affinity sensors based on conducting polymers 15.1.6.6 Possible exploitation of biocompatibility of conducting polymers for the design of implantable affinity sensors 15.2 Conclusions Funding Conflicts of interest References 16 Molecularly imprinted biosensors for sensitive detection of biomarkers 16.1 Introduction 16.2 Biomarkers 16.2.1 Disease-related biomarkers and drug-related biomarkers 16.3 Molecularly imprinting technology 16.3.1 Polymeric materials 16.3.2 Imprinting technology 16.3.2.1 Traditional imprinting methods 16.4 Surface imprinting 16.4.1 Microcontact imprinting 16.4.1.1 Immobilizing the template on a surface 16.4.1.1.1 Surface grafting 16.4.1.1.2 Epitope imprinting 16.4.1.2 Aptamer-molecularly imprinted polymer 16.4.1.3 Metal-chelating 16.4.1.4 Electropolymerization 16.5 Electrochemical transduction 16.6 Voltammetry/amperometry 16.7 Potentiometry 16.7.1 Ion-selective electrode systems 16.7.2 Field-effect transistor systems 16.8 Capacitance/impedance 16.9 Optical sensors 16.9.1 Surface-enhanced Raman scattering 16.9.2 Phosphorescence 16.9.3 Chemiluminescence sensing 16.9.4 Colorimetric sensing 16.9.5 Fluorescence sensing 16.10 Piezoelectric sensors 16.11 Conclusion References 17 Microfluidics technology: past, present, and future prospects for biomarker diagnostics 17.1 General introduction 17.1.1 Explanation of microfluidics 17.1.2 Basics of microfluidics 17.2 Type of microfluidics system 17.2.1 Droplet-based microfluidics 17.2.1.1 Mechanism of droplet generation 17.2.1.2 Mixing in droplet 17.2.2 Digital microfluidic 17.2.2.1 Fabrication 17.2.3 Paper-based microfluidic 17.2.3.1 Paper substrates 17.2.4 Continuous flow microfluidics 17.2.5 Open microfluidics 17.2.5.1 Physical restriction 17.2.5.2 Wettability-contrast restriction 17.2.5.3 Open microfluidic capillary devices 17.3 Application of microfluidic system 17.3.1 3D-printing microfluidics 17.3.2 Biomedical 17.3.3 Pathogen sensing 17.3.4 Optical detection 17.3.4.1 Integration of optical functions: on-chip approach 17.4 Future and perspectives References 18 Wearable biosensors for monitoring of disease-related biomarkers 18.1 Introduction 18.2 Wearable (bio)devices for monitoring of disease biomarkers 18.3 Wearable optical (bio)sensors 18.4 Wearable electrochemical biosensors 18.5 Opportunities, challenges, concerns, and future prospects Acknowledgments References 19 Nanomachines and nanorobotics: improving cancer diagnosis and therapy 19.1 Introduction 19.2 Nanomachines at a glance 19.2.1 Propulsion methods 19.2.1.1 Self-propelled nanomachines 19.2.1.2 Externally propelled nanomachines 19.2.1.3 Hybrid actuation 19.2.2 Design and fabrication techniques 19.3 Nanodevices in cancer diagnosis and imaging 19.3.1 Cancer diagnosis 19.3.1.1 Light energy propelled nanomachines applied in cancer diagnosis 19.3.1.2 Living object propelled nanodevices in cancer diagnosis 19.3.1.3 Chemically propelled nanodevices applied in cancer diagnosis 19.3.1.4 Magnetically propelled nanodevices in cancer diagnosis 19.3.1.5 Ultrasound propelled nanodevices in cancer diagnosis 19.3.2 Cancer imaging 19.3.2.1 Magnetic resonance imaging-based nanodevices 19.3.2.2 Fluorescence imaging-based nanodevices 19.3.2.3 Photoacoustic imaging-based nanodevices 19.3.2.4 Computed tomography imaging-based nanodevices 19.4 Nanomachines in active cancer drugs delivery 19.4.1 In vitro cancer drugs delivery 19.4.2 In vivo active anticancer drugs delivery 19.5 Nanomachines and nanorobots for cancer theragnostic 19.5.1 Micro and nanoparticles-based cancer theragnostic micro/nanodevices 19.5.2 Nucleic acid-based cancer theragnostic nanodevices 19.5.3 Red blood cells-based cancer theragnostic nanodevices 19.6 Nanosurgery 19.7 Conclusion and future prospects Acknowledgments References 20 Analytical perspective on biomarkers research: from untargeted to targeted metabolomics 20.1 Introduction 20.2 Krebs cycle targeted pathway analysis 20.2.1 Analysis of the Krebs cycle intermediates 20.2.2 Gas chromatography 20.2.3 Liquid chromatography 20.3 Sulfur pathway 20.3.1 Analysis of sulfur pathway metabolites 20.4 Phosphonucleotides 20.4.1 Analysis of phosphonucleotide pathway metabolites 20.5 Validation of targeted metabolomic analysis 20.6 Conclusion References Index Back Cover