Molecular Diagnostics - Technologies, Markets and Companies

Table of Contents

Part I: Technologies & Applications

0. Executive Summary  

1. Introduction 

• Definitions and scope of the subject 
• Historical evolution of molecular diagnostics
• Molecular biology relevant to molecular diagnostics
• DNA 
• DNA polymerases
• Restriction endonucleases 
• RNA 
• RNA polymerases 
• Non-coding RNAs 
• DNA transcription
• Chromosomes 
• Chromatin 
• Extrachromosomal DNA 
• Telomeres
• Mitochondrial DNA 
• Genes
• The genetic code 
• Gene expression  
• The human genome  
• ENCODE 
• Variations in the human genome
• Variations in DNA sequences 
• Single nucleotide polymorphisms 
• Haplotyping 
• Copy number variations in the human genome  
• Genotype and haplotypes 
• Genomic imprinting 
• Insertions and deletions in the human genome  
• Complex chromosomal rearrangements 
• Large scale variation in human genome 
• Structural variations in the human genome 
• Replication of the DNA helix 
• Transposons 
• Epigenetics/epigenomics  
• DNA methylation 
• Proteins 
• Proteomics 
• Monoclonal antibodies  
• Aptamers  
• Basics of molecular diagnostics 
• Tracking DNA: the Southern blot  
• Pulsed-field gel electrophoresis 
• DNA Probes 
• The polymerase chain reaction  
• Basic Principles of PCR
• Target selection 
• Detection of amplified DNA
• Impact of human genome project on molecular diagnostics 
• Mapping and sequencing of structural variation from human genomes 
• 1000 Genomes Project 
• Human Variome Project 
• Role of bioinformatics in molecular diagnostics 
• Systems biology approach to molecular diagnostics 
• Synthetic biology and molecular diagnostics 
• Biomarkers 
• Applications of molecular diagnostics 

2. Molecular Diagnostic Technologies 

• Introduction 
• DNA sample collection and extraction
• Blood samples 
• Buccal swabs and saliva
• Dried blood spots 
• Formalin-fixed, paraffin-embedded tissues 
• Manual vs automated DNA extraction  
• Urine samples for transrenal DNA 
• Sample preparation 
• Pressure Cycling Technology  
• Membrane immobilization of nucleic acids
• Automation of sample preparation in molecular diagnostics
• ABI PRISM 6700 Automated Nucleic Acid Workstation 
• BioRobot technology 
• COBAS AmpliPrep System 
• GENESIS FE500 Workcell 
• GeneMole 
• PCR BioCube 
• QIAsymphony 
• Tigris instrument system 
• Techniques for sample preparation suitable for automation  
• Xtra Amp Genomic DNA Extraction 
• Extraction of DNA from paraffin sections  
• Dynabead technology 
• SamPrep
• Use of magnetic particles for automation in genome analysis  
• Companies involved in nucleic acid isolation  
• Labeling and detection of nucleic acids
• Novel PCR methods
• Addressing limitations of PCR 
• ARMS-PCR 
• CAST-PCR 
• Combined PCR-ELISA 
• Convection PCR  
• Co-Dx PCR 
• Digital PCR
• Dumbbell PCR 
• Emulsion PCR  
• ExCyto PCR  
• Fast PCR 
• Immuno PCR 
• Long and accurate PCR 
• Multiplex PCR  
• Overlap extension PCR 
• Real-time PCR systems 
• Dyes used in real-time PCR  
• Target-specific fluorogenic probes for monitoring real-time PCR
• Applications of real-time PCR
• Limitations of real-time PCR 
• Quantitative PCR for accurate low level DNA analysis. 70 qPCR for quantification of mtDNA
• Real-time qPCR for measuring the length of telomeres 
• Guidelines for real-time qPCR  
• Future applications of real-time qPCR 
• Commercially available real-time PCR systems 
• Life Technologies’ Real-Time PCR systems
• LightCycler PCR system 
• LightUp probes based on real-time PCR 
• PlexPCR based on PlexZyme technology
• READ™ real-time PCR method 
• StellARray™ technology 
• Reverse hybridization PCR assays 
• Reverse transcriptase (RT)-PCR 
• Standardized reverse transcriptase PCR 
• Single cell PCR
• LATE-PCR
• COLD-PCR 
• AmpliGrid-System 
• Solar thermal PCR system monitored by Smartphone 
• Ultrafast photonic PCR  
• DNA melt analysis
• High-resolution DNA melt analysis for genotyping 
• PCR device for DNA melt analysis in space 
• Monitoring of gene amplification in molecular diagnostics 
• Non-PCR nucleic acid amplification methods 
• DNA probes with conjugated minor groove binder 
• DNAble  
• Dynamic Flux Amplification 
• Isothermal nucleic acid amplifications 
• Isothermal reaction for amplification of oligonucleotides 
• Isothermal and chimeric primer-initiated amplification of nucleic acids
• Loop-mediated amplification
• Single Primer Isothermal Amplification 
• Strand Invasion Based Amplification 
• Linked Linear Amplification 
• Multiplex Ligation-Dependent Probe Amplification 
• Rapid analysis of gene expression 
• Recombinase polymerase amplification 
• Rolling circle amplification technology 
• Gene-based diagnostics through RCAT 
• RCAT-immunodiagnostics 
• RCAT-pharmacogenomics 
• Circle-to-circle amplification 
• Ramification amplification method
• Transcription mediated amplification 
• WAVE nucleic acid fragment analysis system 
• Technologies for signal amplification
• 3 DNA dendrimer signal amplification  
• Hybridization signal amplification method  
• Signal mediated amplification of RNA technology 
• Invader assays 
• Hybrid Capture technology  
• Branched DNA test
• Tyramide signal amplification 
• Non-enzymatic signal amplification technologies  
• Non-PCR methods for molecular diagnosis 
• Direct molecular analysis without amplification 
• Trilogy™ Platform 
• Direct detection of dsDNA 
• Multiplex assays 
• Fluorescent in situ hybridization
• FISH technique 
• Applications of FISH  
• Modifications of FISH
• Direct visual in situ hybridization  
• Direct labeled Satellite FISH probes 
• Comparative genomic hybridization  
• Primed in situ labeling 
• Interphase FISH  
• FISH with telomere-specific probes 
• Multicolor FISH 
• Simultaneous Ultrasensitive Subpopulation staining/Hybridization In situ 
• Automation of FISH
• Companies involved in FISH diagnostics
• RNA diagnostics
• RNA isolation from tissue samples 
• Commercially available tests for mRNA detection and quantitation  
• Branched-chain DNA assay for measurement of RNA 
• Cycling probe technology  
• Invader RNA assays 
• Linear RNA amplification 
• Non-isotopic RNase cleavage assay 
• Nucleic acid sequence-based amplification  
• Q Beta replicase system 
• RNAScope  
• RNA expression profiling 
• Visualization of mRNA expression in vivo  
• Solid Phase Transcription Chain Reaction 
• Transcriptome analysis  
• MicroRNA diagnostics 
• Microarray vs quantitative PCR for measuring miRNAs  
• Microarrays for analysis of miRNA gene expression 
• miR-TRAP to identify miRNA targets in vivo  
• Modification of in situ hybridization for detection of miRNAs 
• Nuclease Protection Assay to measure miRNA expression
• Real-time PCR for expression profiling of miRNAs
• Use of LNA to explore miRNA
• Whole genome amplification
• Companies that provide technologies for whole genome amplification
• QIAGEN’s Repli-G system
• GenomePlex Whole Genome Amplification 
• DNA sequencing
• Applications of next generation sequencing in molecular diagnostics  
• Companies developing sequencing for molecular diagnostics 
• Molecular diagnostics and sequencing in space  
• Genome-wide approach for chromatin mapping 
• Mitochondrial sequencing 
• Identification of unknown DNA sequences 
• Mitochondrial exome sequencing 
• Optical mapping
• Gene expression analysis
• Gene expression profiling on whole blood samples 
• Gene expression patterns of white blood cells
• Gene expression profiling based on alternative RNA splicing  
• MAUI (MicroArray User Interface) hybridization 
• Monitoring in vivo gene expression by molecular imaging  
• Serial analysis of gene expression (SAGE)
• Single-cell gene expression analysis  
• T cell receptor expression analysis 
• Tangerine™ expression profiling 
• Whole genome expression array 
• Ziplex™ system 
• Companies involved in gene expression analysis 
• Peptide nucleic acid technology 
• Use of PNA with fluorescence in situ hybridization 
• PNA and PCR 
• Use of PNA with biosensors  
• PNA-based PD-loop technology 
• PNA-DNA hybrid quadruplexes
• Companies involved in PNA diagnostics
• Locked nucleic acids 
• Zip Nucleic Acids
• Electrochemical detection of DNA 
• Mediated nucleic acid oxidation
• Detection of hybridized nucleic acid with cyclic voltametry 
• Electrochemical detection based on Toshiba’s CMOS technology
• Electrochemical detection of DNA for POC 
• Concluding remarks on electrochemical DNA detection 
• Bead-based assay platforms 
• Amplification Refractory Mutation System 
• Nucleic acid lateral flow molecular diagnostics
• Omics-based tests 

3. Biochips, Biosensors, and Nanobiotechnology  

• Introduction to biochip technology 
• Applications of biochips in diagnostics 
• GeneChip
• GeneChip Human Genome Arrays 
• AmpliChip CYP
• Electronic detection of nucleic acids on microarrays 
• Microchip capillary electrophoresis 
• Strand displacement amplification on a biochip  
• Rolling circle amplification on microarrays 
• LiquiChip-RCAT 
• Fast PCR biochip  
• Multiplex microarray-enhanced PCR for DNA analysis  
• Multiplexed Molecular Profiling 
• Universal DNA microarray combining PCR and ligase detection reaction 
• Genomewide association scans 
• Whole genome chips/microarrays
• Transposon insertion site profiling chip 
• Standardizing the microarrays 
• Companies involved in developing biochip technology for diagnostics 
• Future of biochip technology for molecular diagnostics
• Microfluidic chips 
• Fish-on-chip  
• Lab-on-a-chip
• LabCD 
• Micronics' microfluidic technology
• Microfluidic chips/arrays using PCR 
• Microfluidic automated DNA analysis using PCR  
• Digital PCR Array  
• Digital PCR on a SlipChip 
• Microfluidic chips integrated with RCAT 
• Microfluidic chips integrated with PET 
• Companies developing microfluidic technologies 
• Biosensor technologies 
• Classification of biosensor technologies
• DNA-based biosensors 
• DNA hybridization biosensor chips
• PCR-free DNA biosensors 
• DNA based biosensor to detects metallic ions  
• Genetically engineered B lymphocytes  
• Biosensors immunoassays
• PNA (peptide nucleic acid)-based biosensors  
• Protein-based biosensors  
• Antibody biosensors 
• Cell-based biosensors (cytosensors)  
• Multicell biosensors  
• Microbial biosensors 
• Optical biosensors 
• Surface plasmon resonance technology 
• Label-free optical biosensor
• Electrochemical sensors 
• Enzyme electrodes for biosensing 
• Conductometric sensors 
• Electrochemical genosensors 
• Electrochemical nanobiosensor 
• Electrochemical microRNA biosensor  
• Phototransistor biochip biosensor 
• Ribozyme-based sensors
• RiboReporters
• Wearable biosensors 
• Concluding remarks and future of biosensor technology 
• Companies developing biosensors for molecular diagnostics  
• Molecular labels and detection
• Detection technologies for molecular labels 
• Fluorescence and chemiluminescence 
• Fluorescence technologies for label detection
• Companies with fluorescence and chemiluminescence products 
• Molecular beacons
• The Green fluorescent protein 
• Multiophoton detection radioimmunoassay  
• Multi-pixel photon counter 
• Enzyme labels and detection by fluorescence 
• Phase-sensitive flow cytometry
• Microtransponder-based DNA diagnostics 
• Laboratory Multiple Analyte Profile 
• Multiple labels  
• Protein-DNA chimeras for detection of small numbers of molecules
• Single molecule detection 
• Atomic force microscopy 
• Capillary electrophoresis 
• Confocal laser scanning 
• Time domain optical imaging technology 
• nCounter Analysis System
• Spectrally resolved fluorescence lifetime imaging microscopy 
• Molecular imaging 
• Technologies for molecular imaging
• Positron emission tomography  
• Magnetic resonance imaging 
• Optoacoustic imaging  
• Computer tomography
• Hyperpolarized diazirines for in vivo biomolecular imaging  
• Basic research in molecular imaging  
• Devices for molecular imaging 
• Molecular imaging in clinical practice 
• Companies involved in molecular imaging 
• Nanobiotechnology for molecular diagnostics
• Cantilever arrays 
• Diagnostics based on nanopore technology 
• DNA nanomachines for molecular diagnostics 
• Exosome-based molecular diagnostics  
• Fullerene photodetectors for chemiluminescence detection on microfluidic chip
• Gold nanoparticles  
• Immunoliposome-PCR 
• Magnetic nanoparticles  
• Nanotechnology on a chip 
• NanoChip® Electronic Microarray
• Nanobarcodes technology for molecular diagnostics 
• Nanosensors 
• Detection of cocaine molecules by nanoparticle-labeled aptasensors
• Nanosensors for glucose monitoring 
• PEBBLE nanosensors 
• Quartz nanobalance biosensor  
• DNA nanoswitch-linked immunosorbent assay 
• Quantum dot technology
• Qdot nanobarcode for multiplexed gene expression profiling
• Resonance Light Scattering technology 
• Role of nanobiotechnology in improving molecular diagnostics  
• Companies involved in nanomolecular diagnostics 
• Concluding remarks about nanodiagnostics 
• Future of nanodiagnostics 

4. Proteomic Technologies for Molecular Diagnostics 

• Introduction 
• Proteomic technologies 
• Biomarkers of disease 
• Proteomic tools for biomarkers 
• Search for biomarkers in body fluids
• Captamers with proximity extension assay for proteins
• Cyclical amplification of proteins 
• Detection of misfolded proteins by ELISA with exponential signal amplification 
• Detection of proteins by Western blot 
• Diagnostics based on designed repeat proteins  
• Differential Peptide Display  
• Light-switching excimer probes
• MALDI-TOF MS 
• Molecular beacon aptamer 
• Molecular beacon assay 
• Proteomic patterns 
• Real-time PCR for protein quantification
• Protein biochip technologies
• ProteinChip 
• LabChip for protein analysis 
• TRINECTIN proteome chip
• Protein chips for antigen-antibody interactions molecular diagnostics 
• Microfluidic devices for proteomics-based diagnostics  
• Nanotechnology-based protein biochips/microarrays 
• Nanoparticle protein chip 
• Protein nanobiochip 
• New developments in protein chips/microarrays 
• Antibody microarrays  
• Aptamer-based protein biochip 
• Multiplexed Protein Profiling on Microarrays 
• Proteomic pattern analysis 
• Single molecule array  
• Viral protein chip  
• Commercial development of protein chips for molecular diagnostics 
• Proteome Identification Kit 
• Laser capture microdissection (LCM) 
• LCM technology 
• Applications of LCM in molecular diagnostics  
• Proteomic diagnosis of CNS disorders
• Cerebrospinal fluids tests based on proteomics  
• Urine tests for CNS disorders based on proteins in urine 
• Diagnosis of CNS disorders by examination of proteins in the blood
• Diagnosis of CNS disorders by examination of proteins in tears
• Role of proteomics in the diagnosis of Alzheimer's disease 
• Role of proteomics in the diagnosis of Creutzfeldt-Jakob disease 
• Future of use of proteomics for diagnosis of CNS disorders
• Concluding remarks on the use of proteomics in diagnostics

5. Molecular Diagnosis of Genetic Disorders 

• Introduction 
• Cytogenetics 
• FISH with probes to the telomeres 
• Single copy FISH probes 
• Comparative genomic hybridization 
• Use of biochips in genetic disorders
• Representational oligonucleotide microarray analysis
• Diagnosis of genomic rearrangements by multiplex PCR 
• Quantitative fluorescent PCR 
• Mutation detection technologies 
• PCR-based methods for mutation detection 
• Cleavase Fragment Length Polymorphism 
• Direct dideoxy DNA sequencing 
• Digital Genetic Analysis (DGA)  
• Fluorescence-based directed termination PCR  
• Fluorescence melting curve analysis for multiplex mutation detection  
• Heteroduplex analysis 
• Restriction fragment length polymorphism 
• Single-stranded conformation polymorphism (SSCP) analysis 
• TaqMan real-time PCR 
• Non-PCR methods for mutation detection
• Arrayed primer extension
• BEAMing (beads, emulsion, amplification, and magnetics)
• ELISA-protein truncation test 
• Enzymatic mutation detection
• Specific anchor nucleotide incorporation 
• Conversion analysis for mutation detection  
• Biochip technologies for mutation detection
• Combination of FISH and gene chips  
• Haplotype Specific Extraction 
• Use of biosensors for detection of mutations  
• Technologies for SNP analysis 
• Acoustic detection of DNA conformation in genetic assays combined with PCR 
• DNA sequencing  
• Electrochemical DNA probes 
• Use of NanoChip for detection of SNPs
• Laboratory Multiple Analyte Profile 
• Pathway enrichment and network analysis of GWAS 
• PCR-CTPP (confronting two-pair primers)
• PCR using one primer amplification of PCR-CTPP products 
• Peptide nucleic acid probes for SNP detection 
• Pyrosequencing 
• Reversed enzyme activity DNA interrogation test  
• Single base extension-tag array 
• Smart amplification process version 2  
• SNP genotyping on a genome-wide amplified DOP-PCR template 
• SNP genotyping with gold nanoparticle probes
• UCAN method (Takara Biomedical)
• Zinc finger proteins 
• Biochip and microarray-based detection of SNPs
• SNP genotyping by MassARRAY  
• Electronic dot blot assay 
• Biochip combining BeadArray and ZipCode technologies 
• SNP-IT primer-extension technology 
• SNaPshot® Multiplex System for SNP genotyping 
• Affymetrix SNP genotyping array 
• Concluding remarks on SNP genotyping 
• Limitations of SNP in genetic testing 
• Haplotyping versus SNP genotyping  
• Nanofluidics technology for high throughput SNP genotyping
• Companies involved in developing technologies/products for SNP analysis 
• Role of copy number variations in genetic diagnostic testing 
• CNVs in various diseases  
• CNVs in genetic epilepsy syndromes
• CNVs associated with schizophrenia 
• Methods for determination of CNVs 
• Digital array for CNV detection 
• Wellcome Trust Case Control Consortium CNV typing array 
• CNVer algorithm for CNV detection 
• CNVnator for discovery of CNVs and genotyping 
• Study of rare variants in pinpointing disease-causing genes  
• Chromothripsis and congenital abnormalities 
• Role of reanalysis of genomic sequence data in genetic diagnosis
• Role of whole genome sequencing in screening of newborns 
• Prenatal DNA diagnosis 
• Invasive prenatal diagnostic procedures  
• Amniocentesis 
• Chorionic villus sampling
• Molecular methods for prenatal diagnosis
• aCGH for prenatal diagnosis  
• BAC HD Scan test 
• FISH for prenatal diagnosis 
• PCR for prenatal diagnosis 
• In vivo gene expression analysis of the living human fetus 
• Non-invasive prenatal molecular diagnostic procedures  
• Fetal cells separation from maternal blood for genetic diagnosis 
• Digital relative mutation dosage in maternal plasma 
• Prenatal testing based on transrenal DNA from urine 
• Reflex DNA screening protocol  
• Tests for preterm birth 
• Tests on fetal DNA in maternal blood
• Sequencing-based methods for prenatal diagnosis from maternal DNA 
• cfDNA testing vs routine screening in first trimester of pregnancy 
• Noninvasive WGS of the fetus
• Directed DNA analysis of maternal blood
• Applications of prenatal diagnosis  
• Antenatal screening for Down's syndrome 
• Diagnosis of congenital infections
• Diagnosis of eclampsia 
• Identification of cancers in pregnant women during NIPT 
• Preimplantation genetic diagnosis 
• Technologies for preimplantation genetic diagnosis  
• PCR for preimplantation genetic diagnosis 
• FISH for preimplantation genetic diagnosis
• Microarrays for preimplantation genetic diagnosis  
• Whole genome sequencing for PGD 
• Conditions detected by preimplantation genetic diagnosis  
• The future of preimplantation genetic diagnosis 
• Companies involved in prenatal/preimplantation diagnosis 
• Cystic fibrosis 
• Detection of CFTR gene mutations 
• CFTR technologies of various companies  
• Asuragen's bead array test
• Ambry CF Test
• Biochip for CF diagnosis  
• CF Plus Tag-It Cystic Fibrosis Kit  
• HerediT™ (SEQUENOM) CF carrier screening test 
• Identification of CF variants by PCR/Oligonucleotide Ligation Assay  
• LabCorp's CF gene sequencing 
• MiSeqDx sequencing-based CF assays 
• Serum proteomic signature for CF using antibody microarrays 
• Guidelines for genetic screening for CF 
• Congenital adrenal hyperplasia
• Primary immunodeficiencies
• Hematological disorders 
• Hemoglobinopathies 
• Sickle cell anemia 
• Thalassemia 
• Paroxysmal nocturnal hemoglobinuria
• Hemophilia
• Hereditary hemochromatosis 
• Polycystic kidney disease 
• Hereditary metabolic disorders
• Lesch-Nyhan Syndrome 
• Gaucher’s Disease
• Acute Intermittent Porphyria 
• Phenylketonuria
• Hereditary periodic fever
• Achondroplasia 
• Molecular diagnosis of eye diseases 
• Molecular diagnosis of retinitis pigmentosa 
• Genetic screening for glaucoma  
• Role of molecular diagnostics in rheumatoid arthritis
• Molecular diagnosis of neurogenetic disorders 
• Alzheimer's disease 
• Autism spectrum disorders
• CNVs associated with autism 
• Charcot-Marie Tooth disease 
• Down syndrome
• Duchenne and Becker muscular dystrophy  
• eNOS gene polymorphisms as predictor of cerebral aneurysm rupture 
• Fragile X syndrome 
• Huntington disease 
• Hereditary neuropathy with liability to pressure palsies
• Mitochondrial disorders affecting the nervous system  
• Parkinson’s disease 
• Pompe’s disease  
• Spinal muscular atrophy 
• Triple repeat disorders
• Genetic testing for disease predisposition 
• Direct-to-consumer genetic tests 
• Genetic diagnosis in patients with previously undiagnosed disease 

6. Molecular diagnosis of cardiovascular disorders  

• Introduction 
• Coronary heart disease 
• Genomics of coronary heart disease  
• Diagnosis of coronary artery disease based on gene expression 
• Cardiomyopathy
• Hypertrophic cardiomyopathy  
• Idiopathic dilated cardiomyopathy 
• Cardiac arrhythmias 
• Genetic tests for cardiac arrhythmias 
• Long Q-T syndrome
• Familial atrial fibrillation
• Idiopathic ventricular fibrillation 
• Congestive heart failure
• Hypertension 
• Disturbances of blood lipids
• Familial dyslipoproteinemias
• Hypercholesterolemia 
• Thrombotic disorders
• Factor V Leiden mutation  
• Pulmonary embolism  
• Hereditary thrombophilia  
• Molecular diagnostics for monitoring heart transplant rejection
• AlloMap® molecular expression testing
• Commercial molecular diagnostics for cardiovascular disorders 

7. Molecular Diagnosis of Infections 

• Introduction 
• Molecular techniques for the diagnosis of infections 
• Antibody-enhanced microplate hybridization assays 
• Bacteriophage-based methods for detection of bacteria  
• Biochips/microarrays for detection of microorganisms 
• Lawrence Livermore Microbial Detection Array 
• Biosensors for detection of microorganisms
• Ibis T5000™ Biosensor System 
• Molecular Mirroring Technology
• DNA enzyme immunoassay  
• DNA biochip/microarray in diagnosis of infections 
• DNA-based typing methods  
• Restriction fragment length polymorphism analysis 
• Ribotyping  
• Random amplified polymorphic DNA 
• Combinatorial DNA melting assay
• Electrochemical detection of pathogens 
• Field Activated Sample Treatment (FAST) 
• FISH for detection of infections 
• hemoFISH assay 
• Helicase-dependent isothermal amplification for rapid detection of pathogens 
• High resolution melt analysis for diagnosis of infections  
• Immunomagnetic cell capture 
• Ligase chain reaction 
• MRI for diagnosis of infections 
• Multiplex PCR for detection of infections
• Metagenomic pyrosequencing  
• Dual priming oligonucleotide for multiplex PCR 
• Multiplex amplified nominal tandem repeat analysis  
• Nanopore-based diagnosis of infections 
• NASBA for detection of microorganisms 
• Nucleic acid probes 
• Neutrophil CD11b expression as a diagnostic marker
• Optical Mapping 
• PCR electrospray ionization mass spectrometry 
• PNA-FISH for diagnosis of infections  
• Proteomic technologies for diagnosis of infections 
• Mass spectrometry for microbial identification 
• QuantiFERON® technology for pre-molecular diagnosis of infections  
• Quantitative reverse-transcription PCR for bacterial diagnostics 
• Rapid electrochemical diagnosis of infections  
• Rupture event scanning 
• Real-time single-molecule imaging of virus particles
• Single-strand conformational polymorphism 
• SmartGene platform for identifying pathogens based on genetic sequences 
• Tessera array technology  
• Tests for sepsis
• LightCycler® SeptiFast Test  
• NanoDx™
• Next-generation sequencing assay to detect cell-free microbial DNA
• SeptiCyte Triage assay 
• SepsiTest™ 
• VYOO® Sepsis Test 
• Unyvero Solution 
• Applications, advantages and limitations of molecular diagnostics
• Molecular diagnostics versus other microbial detection technologies 
• Advantages of nucleic acid-based diagnostics in infections 
• Drawbacks of nucleic acid-based diagnostics in infections  
• Nanotechnology for detection of infectious agents 
• Bacterial infections 
• Mycobacterium tuberculosis 
• Conventional diagnosis of tuberculosis 
• Combined tuberculin skin testing and ELISpotPLUS assay 
• Microscopic Observation Drug Susceptible Assay for tuberculosis  
• Molecular diagnostics for tuberculosis 
• Diagnosis of TB in a POC setting  
• Diagnosis of drug-resistant MTB infection 
• Gene expression blood test for detecting TB 
• GeneXpert MTB/RIF (eXpert) automated molecular test for MTB 
• QuantiFERON-TB Gold test 
• Transcriptional signatures in active vs asymptomatic tuberculosis 
• Diagnosis of other mycobacteria 
• Leprosy and M. leprae 
• Bacteria associated with bacterial vaginosis
• Chlamydial infections 
• Neisseria gonorrhoeae 
• Trichomonas vaginalis 
• Streptococcal infections 
• Group B Streptococci
• Group A Streptococcus and Streptococcus dysgalactiae 
• Pseudomonas aeruginosa 
• Helicobacter pylori  
• Vibrio Cholerae 
• Lyme disease 
• Mycoplasmas
• Fungal infections 
• PCR-based tests for fungal infections
• DNA barcode marker for fungi 
• DNA sequencing for fungal infections
• MALDI-TOF MS for diagnosis of fungal infections 
• Aspergillus 
• Candida species 
• Viral infections
• Carbon nanotubes-based detection of viruses 
• Sensitive metagenomic sequencing for detection of pathogenic human viruses 
• Simultaneous testing of multiple viruses by VirScan 
• FDA-approved molecular diagnostics for viral infections  
• HIV/AIDS
• Diagnosis of HIV 
• Detection of HIV provirus 
• Global Surveillance of HIV-1 genetic variations 
• Genotyping for drug-resistance in HIV 
• Neonatal screening of infants of HIV-positive mothers  
• Phenotyping as predictor of drug susceptibility/resistance in HIV  
• POC testing for HIV  
• PCR for resolution of indeterminate Western blot 
• Screening of cadaveric tissue donors  
• Tests used for quantification of HIV 
• Conclusions about HIV diagnostics  
• Hepatitis viruses  
• Hepatitis A virus 
• Hepatitis B virus 
• Hepatitis C virus 
• Detection and quantification of HCV RNA
• Quantification of HCV RNA levels as a guide to antiviral therapy 
• Electrochemical DNA chip for diagnosis of HCV 
• HCV Genotyping as a guide to therapy
• Hepatitis E  
• Enteroviruses 
• Adenoviruses
• Rhinoviruses 
• Herpes viruses 
• Herpes simplex virus 
• Genital and neonatal herpes simplex  
• Human cytomegalovirus infections  
• Epstein-Barr virus 
• Human papilloma virus  
• Molecular diagnostics for HPV 
• Detection of encephalitis viruses 
• West Nile and St. Louis encephalitis 
• Venezuelan equine encephalitis virus 
• Detection of noroviruses 
• Detection of dengue virus 
• Detection of Ebola virus 
• Detection of Zika virus
• Protozoal infections 
• Amebiasis  
• Cryptosporidium parvum
• Leishmaniasis 
• Malaria 
• Neurocysticercosis  
• Pneumocystis carinii 
• Toxoplasmosis  
• Infections of various systems 
• CNS infections  
• Molecular diagnosis in bacterial meningitis 
• Molecular diagnosis in herpes simplex encephalitis 
• Diagnosis of transmissible spongiform encephalopathies  
• Molecular diagnosis of respiratory viruses 
• Avian influenza H7N9  
• H1N1 influenza  
• Influenza viruses  
• Avian influenza H5N1  
• Coronaviruses 
• Coronavirus China 
• Nucleic acid-based testing for SARS-CoV-
• Detection of variants of SARS-CoV-2  
• COVID-19 diagnostic pipeline 
• Serological assay for detection of SARS-CoV-2 antibodies 
• Progress of EUA of coronavirus diagnostics
• POC diagnostics for COVID-19  
• Tests for SARS-CoV-2 variants 
• FDA’s role in molecular diagnostic testing for COVID-
• Reassessment of molecular diagnostics for COVID-
• Gastrointestinal infections 
• Periodontal infections 
• Diagnosis of urinary infections by a biosensor
• Role of molecular diagnosis in sexually transmitted infections
• Role of molecular diagnostics in septicemia 
• Limitations and needs of diagnostics for infections 
• Cell-based methods for identifying pathogenic microorganisms
• Cell-based virus assays
• Cell-based detection of host response to infection  
• Role of molecular diagnostics in hospital acquired infections 
• Molecular diagnostics for detection of drug resistance in infections  
• Detection of hospital-acquired bacterial infections 
• Detection of methicillin-resistant S. aureus  
• Whole-genome sequencing for investigation of MRSA outbreaks 
• Detection of carbapenemase-producing Gram-negative bacteria 
• Detection of vancomycin-resistant enterococci
• Detection of hospital-acquired C. difficile
• Integrated device for rapid detection of organisms associated HAI 
• Bacterial genome sequencing in antimicrobial resistance 
• Detection of hospital-acquired viral infections 
• Molecular diagnosis of BK virus 
• Diagnosis of hospital-acquired rotavirus gastroenteritis
• Molecular diagnostics and the microbiome 
• Human Microbiome Project
• Application of metagenomics for study of the microbiome  
• MicroBiome Analysis Center 
• Concluding remarks and future of diagnosis of infections
• Rapid point-of-care diagnosis of infections  
• Diagnosis of viruses using protein fingerprinting 
• QIAplex PCR multiplex technology 
• Role of PCR vs sequencing for diagnosis of infections
• Companies involved in molecular diagnosis of infectious diseases 

8. Molecular Diagnosis of Cancer  

• Introduction 
• Cancer genomics
• Cancer genes 
• Oncogenes 
• Tumor Suppressor Genes  
• BRCA mutations413 p53 . 414 p
• CNVs in cancer 
• Allele-specific copy number analysis of tumors 
• Viruses and cancer  
• Detecting viral agents in cancer 
• Conventional cancer diagnosis
• Molecular techniques for cancer diagnosis
• Exosome-based molecular diagnosis of cancer 
• Expression profiling of tumor cells sorted by flow cytometry  
• MicroRNA expression profiling for cancer diagnostics 
• Genome analysis at the molecular level 
• Mutation detection by sequencing  
• Quality control of NGS in oncology 
• Biomarkers in cancer 
• Circulating nucleic acids as potential biomarkers of cancer  
• Circulating nucleosomes in serum of cancer patients 
• Detection of DNA methylation
• eTag assay system for cancer biomarkers 
• HAAH as a biomarker for cancer  
• LigAmp for detection of gene mutations in cancer  
• Methylscape biomarker of cancer 
• Mitochondrial DNA as a cancer biomarker 
• NIPT for detecting biomarkers of gynecological cancers 
• Oncoproteins as biomarkers for cancer  
• Sequencing-based approaches for detection of cancer biomarkers
• Molecular fingerprinting of cancer  
• Fluorescent in situ hybridization 
• Genetic analysis of cancer
• Comparative genomic hybridization in cancer diagnostics
• Loss of heterozygosity 
• Digital karyotyping 
• Gene expression profiles predict chromosomal instability in tumors  
• PCR Techniques 
• Cold-PCR 
• Real-time qPCR for diagnosis of cancer  
• Real-time PCR with myT™ Primer reagents  
• Antibody-based diagnosis of cancer
• Monoclonal antibodies for diagnosis of cancer  
• Recombinant antibodies as a novel approach to cancer diagnosis  
• Combined immunological and nucleic acid tests 
• Combination of MAbs and RT-PCR 
• Immunobead RT-PCR  
• Assays for determining susceptibility to cancer  
• Gene expression profiling in cancer 
• Microarrays for gene expression profiling in cancer
• Serial analysis of gene expression (SAGE)
• Suppression subtractive hybridization 
• Cancer tests based on gene expression profiling 
• Measurement of telomerase activity  
• Liquid biopsy for detection of circulating tumor cells and cfDNA in body fluids 
• ApoStream for POC detection of CTCs
• BEAMing technology for quantification of circulating tumor DNA
• CEE (cell enrichment and extraction) technology
• CellSearch
• CellTracks® AutoPrep® System  
• CTCscope system for detection of CTCs 
• CTChip™ 
• CTC sorting by acoustic waves 
• Detection of circulating tumor DNA 
• Droplet digital PCR for examination of cell free plasma DNA in cancer 
• DNA nanospheres for isolation of CTCs  
• Fiber-optic array scanning technology
• Herringbone-chip for detection of CTCs 
• IsoFlux System 
• Lab-on-chip for the isolation and detection of CTCs 
• MagSweeper  
• Nano-Velcro to capture CTCs for diagnosis of cancer 
• NanoFlares for detection of CTCs 
• Companies developing tests for detection of CTCs  
• Future of detection of cancer cells in blood 
• Epithelial aggregate separation and isolation  
• Proteomic technologies for the molecular diagnosis of cancer 
• Proteomic technologies for tumor biomarkers  
• Affibodies as contrast agents for imaging in cancer 
• Aptamer-based technology for protein signatures of cancer cells
• Aptamer probes for in vivo diagnosis of cancer 
• Aptamers for combined diagnosis and therapeutics of cancer 
• Automated image analysis of nuclear protein distribution 
• Laser capture microdissection in oncology 
• Layered expression scanning 
• Membrane-type serine protease-
• Survivin and molecular diagnosis of cancer  
• Biochip/microarrays for cancer diagnosis 
• Role of DNA microarrays in gene expression profiling 
• Biochip detection of FHIT gene 
• Multiplexed single-cell analysis of FFPE cancer tissue samples  
• Nanobiotechnology for early detection of cancer 
• Detection of nanoparticle self assembly in tumors by MRI 
• Differentiation between normal and cancer cells by nanosensors
• Magnetic nanoparticle probes 
• Quantum dots for early detection of cancer  
• Molecular imaging of cancer 
• In vivo imaging of single cancer cells 
• In vivo molecular imaging of cancer 
• In vivo tumor illumination by adenoviral-GFP  
• PET for in vivo molecular diagnosis of cancer 
• Radiolabeled peptide-based targeting probes for cancer imaging
• Xenon-enhanced MRI  
• Detection of micrometastases 
• Detection of cancer stem cells 
• Detection of origin in cancers of unknown primary 
• Molecular diagnosis of cancers of various organs 
• Brain tumors 
• Molecular diagnostic methods for brain tumors 
• Glioblastoma  
• Circulating microvesicles as biomarkers of glioblastoma 
• Circulating tumor cells in glioblastoma 
• Combination of neuroimaging and microarray analysis in glioblastoma 
• Medulloblastoma
• Multigene predictor of outcome in glioblastoma  
• Oligodendroglioma 
• Advantages and limitations of molecular diagnosis of brain tumors
• Breast cancer 
• Breast cancer genes 
• Circulating tumor cells and nucleic acid biomarkers of breast cancer 
• Genomic profiles of breast cancer 
• Imaging biopsy specimens as alternative to histological examination 
• Microchimerism and breast cancer  
• Molecular diagnostic tests for breast cancer 
• Molecular diagnostics for management of breast cancer 
• Mouse ESC-based assays to evaluate mutations in BRCA
• One step mucleic acid amplification assay for breast sentinel nodes 
• Prognostic testing for of breast cancer 
• Prediction of recurrence in breast cancer for personalizing therapy
• Cervical cancer 
• Colorectal cancer 
• ColoVantage CRC test 
• Detection of familial adenomatous polyposis coli 
• Detection of CRC at precancerous state 
• Detection of circulating tumor cells in CRC 
• Diagnosis of hereditary nonpolyposis CRC 
• Diagnosis of CRC from DNA in stools  
• Droplet Digital™ PCR for detection of KRAS Mutations  
• Early diagnosis of CRC from blood samples  
• Guanylyl cyclase C-based tests for CRC 
• Multitarget stool DNA testing for CRC screening  
• Gastric cancer  
• Head and neck cancer 
• Nanobiochip sensor technique for analysis of oral cancer biomarkers 
• ProteinChip for diagnosis of head and neck cancer 
• Hematological malignancies 
• Chromosome translocations  
• Flow cytometry in diagnosis of leukemia 
• Gene chip technology  
• Hairy-cell leukemia  
• Laboratory assessment of leukemia
• Molecular probes
• Minimal residual disease 
• Molecular diagnosis in myelodysplastic syndromes 
• Screening of gene mutations in chronic myeloproliferative diseases 
• Lung cancer  
• Biomarkers of immune response in lung cancer  
• Early diagnosis of lung cancer
• Gene abnormalities in lung cancer
• Liquid biopsy based on CTCs in lung cancer 
• Methylation profiling of lung cancer 
• Molecular subtyping of lung cancer 
• Prediction of efficacy of chemotherapy
• Melanoma  
• Ovarian cancer 
• Mutation of genes 
• Relevance of genetic testing to management of ovarian cancer 
• Serum biomarkers for early detection of ovarian cancer
• Biomarkers of ovarian cancer 
• Concluding remarks on testing for ovarian cancer  
• Pancreatic cancer
• Proteomic techniques for diagnosis of pancreatic cancer  
• Detection of KRAS mutations in pancreatic cancer 
• Prostate cancer
• Identification of genetic risks for prostate cancer 
• Gene expression analysis of prostate cancer
• Huntingtin Interacting Protein 
• Integrative genomic and proteomic profiling of prostate cancer 
• LCM for diagnosis of prostate cancer  
• Liquid biopsy for prostate cancer patients 
• Mitomic™ prostate test 
• Nanotechnology for early detection of recurrence of prostate cancer 
• PCA3 gene detection in urine
• PCR assay for assessing silencing of protein cadherin 13 gene 
• Prolaris test
• Prostate biopsy for detection of prostatic intraepithelial neoplasia 
• Prostate Core Mitomic Test™ 
• Prostat Health Index 
• Screening of multiple SNPs for risk of prostate cancer  
• Semen testing for prostate cancer biomarkers 
• Serum-protein fingerprinting in prostate cancer  
• Tissue-based epigenetic test for prostate cancer 
• Thyroid cancer 
• Afirma gene expression classifier for inconclusive thyroid biopsies
• Gene expression biomarkers of thyroid cancer 
• Multiple endocrine neoplasia type 2B as risk factor for thyroid cancer  
• miRNA expression profiling in thyroid cancer 
• Urinary bladder cancer  
• Role of molecular diagnostics in the management of cancer 
• Risk assessment and prevention of cancer  
• Role of molecular diagnosis in the design of future cancer therapies 
• Molecular classification of cancer
• Determination of cancer prognosis 
• Prognosis by tumor classification 
• Prognosis by cancer gene expression 
• Selection of anticancer drugs based on molecular diagnosis  
• Integrated genome-wide analysis of cancer for diagnosis and therapy 
• Role of molecular diagnostics in personalized therapy for cancer
• Personalized diagnosis of cancer 
• Pharmacogenetics and cancer therapy  
• Molecular diagnostics as an aid to selection of cancer therapy  
• Drug resistance in cancer 
• Role of organizations in molecular diagnosis of cancer
• Role of NCI in molecular diagnosis of cancer
• Molecular profiling of cancer  
• Cancer Genome Atlas  
• Support for future research in molecular diagnosis of cancer  
• Role of the International Cancer Genome Consortium  
• Future of molecular diagnosis of cancer 
• Companies involved in molecular diagnosis of cancer

9. Molecular Diagnostics in Biopharmaceutical Industry & Healthcare  

• Introduction 
• Molecular diagnostics in biopharmaceutical industry
• Molecular diagnostic technologies and drug discovery  
• Molecular diagnostics and pharmacogenetics  
• Molecular toxicology 
• Gene expression studies for toxicology  
• Toxicogenomics 
• Toxicoproteomics  
• Mitochondrial assays  
• MetaChip/Datachip 
• Molecular diagnostics and pharmacogenomics 
• Molecular diagnostics and therapeutic drug monitoring 
• Applications molecular diagnostics in gene therapy  
• Use of PCR to study biodistribution of gene therapy vectors 
• PCR for verification of the transcription of DNA 
• In situ PCR for direct quantification of gene transfer into cells
• Detection of retroviruses by reverse transcriptase (RT)-PCR 
• Assessment of safety issues of gene transfer
• Quantitative PCR for monitoring the effectiveness of gene therapy 
• Use of FISH for analysis of adeno-associated viral vector integration 
• Monitoring of gene expression by green fluorescent protein
• Quality control of protein therapeutics and vaccines 
• Detection of microbial contamination in biopharmaceutical manufacturing
• Role of PCR in detecting contamination  
• Systems for rapid detection of contaminants 
• Contamination of biopharmaceuticals with prions 
• DNA tagging for control and tracing of drug distribution channels 
• Molecular diagnostics for organ transplantation 
• HLA typing 
• Sequencing for HLA typing 
• Commercial products for transplant molecular diagnostics 
• Post-cardiac transplant patient monitoring for rejection  
• Application of molecular diagnostics in blood transfusion 
• Molecular diagnostics for testing transfusion compatibility  
• Transmission of infections in blood transfusion  
• Molecular tests for screening of blood supply for viruses 
• Commercial molecular diagnostic technologies for blood screening  
• Bridge amplification technology 
• COBAS AmpliScreen HCV and HIV Assays 
• INACTINE 
• NucliSens Extractor system 
• Pall's enhanced Bacteria Detection System
• PCR combined with algorithm method 
• Prions detection in human blood  
• PRISM® automated system  
• Procleix HIV-1/HCV Assay  
• West Nile virus detection in human blood 
• Zika virus screening of US blood donors
• Advantages and limitations of molecular diagnostics for blood screening 
• Molecular epidemiology 
• Molecular epidemiology of genetic diseases 
• Role of CNVs in study of genetic epidemiology 
• Accumulation of CNVs with aging 
• Monogenic versus polygenic disorders 
• Critical issues facing genetic epidemiology 
• Molecular epidemiology of infectious diseases
• Methods and purposes 
• Emerging infections 
• Human vs. non-human infections
• Genetics and susceptibility to infectious disease 
• Molecular epidemiology of cancer
• Molecular epidemiology of p53 gene mutations 
• Molecular epidemiology of link between virus and cancer 
• Molecular epidemiology and cancer prevention 
• SNPs and molecular epidemiology 
• Molecular diagnostics for identification of food-borne pathogens
• Introduction  
• Molecular diagnostic methods used in food-borne infections  
• Limitations of use of molecular probes in food analysis 
• Detection of Listeria-contaminated foods 
• Optical biosensor for detection of Listeria  
• Real-time PCR for detection of Listeria 
• Sequencing for investigation of food-borne Listeria infections 
• Detection of Salmonella 
• MicroSEQ® Salmonella Detection Kit  
• E. Coli detection
• MicroSEQ® E. Coli Detection Kit  
• DuPont Bax system  
• MLG method for detection of multiple STEC strains 
• Detection of rare strains of E. Coli 
• Companies with technologies for food pathogen detection  
• Transmissible spongiform encephalopathies (TSEs)  
• Basis of molecular diagnosis of prion diseases 
• Molecular diagnosis of TSEs
• Companies involved in developing molecular diagnostics for TSEs 
• Detection of genetically modified food
• Molecular diagnostics for detection of doping in sports 
• Screening of synthetic glucocorticosteroids in human urine 
• Detection of gene doping  
• Role of molecular diagnostics in future healthcare 
• Translation of genomic research into genetic testing for healthcare 
• Molecular diagnostics and disease management
• Role of genetic biomarkers in disease management 
• Role of molecular diagnostics in personalized medicine 
• Integrated healthcare 
• Screening 
• Early diagnosis  
• Prevention  
• Therapy based on molecular diagnosis
• Monitoring of therapy  
• Advantages and limitations of integrated healthcare  
• Commercially available systems for integrated healthcare 
• Combination of diagnostics and therapeutics  
• Companion diagnostics 
• Companies involved in companion diagnostics 
• Point-of-care diagnosis  
• Advantages versus disadvantages of POC diagnosis
• Technologies for point-of-care diagnosis 
• Biochips for POC diagnosis 
• CRISPR for POC diagnosis  
• Mobile detection of infections by microfluidic LAMP and smartphone 
• Nanosensors for POC diagnosis 
• POC Diagnostic Initiative
• Paper-based POC diagnostic for infectious diseases 
• Synthetic biomarker-based POC diagnostic for cancer
• Future of POC testing  
• Companies developing POC diagnosis 
• The impact of molecular diagnostics on clinical laboratory practice  

10. Molecular Diagnostics in Forensic Medicine and Biological Warfare 

• Application of molecular diagnostics in forensic medicine 
• Technologies 
• ABO genotyping
• DNA analysis for identification of ancient or historical specimens
• DNA fingerprinting and short tandem repeats  
• DNA processing of forensic samples 
• DNA profiles from fingerprints  
• Fluorescent detection systems  
• Genome wide association studies linking genes to facial features  
• Mitochondrial DNA analysis 
• Next generation sequencing for forensic diagnosis 
• Pressure cycling technology for forensic applications 
• Polymorphic Alu insertions 
• SNP analysis  
• Applications  
• Applications in criminology 
• Identification of remains of military personnel 
• Identification of remains of victims of mass disasters 
• Parentage testing 
• Gender determination 
• Companies developing molecular diagnostics for forensic science 
• Molecular detection of biological warfare agents 
• Introduction to biological warfare agents 
• Role of PCR in the diagnosis of biological warfare agents
• Multiplex PCR microarray assay to detect bioterror pathogens in blood 
• Laboratory diagnosis of Anthrax 
• Challenges in diagnosis of biological warfare agents 
• US government efforts for detection of biological warfare agents 
• The US Army Medical Research Institute of Infectious Diseases 
• Homeland Security Advance Research Projects Agency 
• Handheld Isothermal Silver Standard Sensor 
• Hapten mediated display and pairing of rAbs for biothreat assays 
• Commercial development of diagnostic devices for biological agents
• Companies developing diagnostic devices for biological agents  
• Various devices for testing 
• Airborne bacterial spore detection technology 
• Analyte 2000 biosensor  
• Bead ARray Counter 
• Benchtop living cell biosensor 
• BioThreat Alert Test Strip
• BioForce NanoArray sensor technology  
• Biodefence microarray 
• Biosensor based on mass spectrometry of microorganisms's RNA 
• Destruction and detection of anthrax by lysin  
• Hand-Held Advanced Nucleic Acid Analyzer  
• Identification of genetic markers of individual pathogens 
• Microbial Identification System based on OptiChip™  
• MicroChemLab 
• Nanode Array Sensor Microchips  
• ProteinChip-based detection of bioterroism agents 
• QTL handheld biosensor 
• TIGER biosensor 
• The PathAlert Detection System 
• VereThreat™  
• Concluding remarks about biodefense applications of diagnostics 

11. References 

Tables

Table 1-1: Landmarks in development of molecular technology and its application to diagnosis 
Table 1-2: Applications of molecular diagnostics 
Table 2-1: Companies with products for nucleic acid isolation
Table 2-2: Applications of real-time PCR  
Table 2-3: Some commercially available real-time PCR systems  
Table 2-4: A selection of companies with commercially available FISH diagnostics  
Table 2-5: Selected companies with RNA diagnostic tests 
Table 2-6: Companies involved in whole genome amplification  
Table 2-7: Companies involved in application of sequencing in molecular diagnostics 
Table 2-8: Comparison of methods of identification of unknown DNA sequences  
Table 2-9: Classification of methods of gene expression analysis  
Table 2-10: A selection of companies with gene expression technologies 
Table 2-11: Companies involved in developing PNA diagnostics 
Table 2-12: Companies with bead-based diagnostic assay platforms 
Table 2-13: Companies developing nucleic acid lateral flow molecular diagnostics
Table 3-1: Applications of biochip technology in relation to molecular diagnostics 
Table 3-2: Companies developing whole genome chips/microarrays 
Table 3-3: Companies involved in biochips for molecular diagnostics 
Table 3-4: Companies developing microfluidic technologies
Table 3-5: Biosensor technologies with potential applications in molecular diagnostics  
Table 3-6: Important applications of biosensors 
Table 3-7: Companies involved in application of biosensors in molecular diagnostics  
Table 3-8: Selected labels for nucleic acid detection 
Table 3-9: Selected companies with fluorescence and chemiluminescence products 
Table 3-10: Companies involved in molecular beacon manufacture and research 
Table 3-11: Selected companies involved in molecular imaging 
Table 3-12: Nanotechnologies with potential applications in molecular diagnostics  
Table 3-13: Companies developing nanomolecular diagnostics  
Table 4-1: Applications of protein biochips/microarrays 
Table 4-2: Companies involved in developing diagnostic applications of protein biochips
Table 4-3: Disease-specific proteins in the cerebrospinal fluid of patients
Table 5-1: Mutation detection technologies  
Table 5-2: Technologies for SNP analysis  
Table 5-3: A sampling of companies involved in technologies for SNP genotyping 
Table 5-4: Application of preimplantation genetic diagnosis in monogenic disorders 
Table 5-5: Companies involved in prenatal/preimplantation diagnostics 
Table 5-6: CFTR genotyping in cystic fibrosis  companies and technologies 
Table 5-7: X-linked immunodeficiency disorders 
Table 5-8: Available molecular diagnostics for neurogenetic diseases  
Table 5-9: Companies offering genetic screening tests directly to consumers 
Table 6-1: Genes that cause cardiovascular diseases 
Table 6-2: Molecular diagnostics for cardiovascular diseases: commercial development 
Table 7-1: Molecular techniques for the diagnosis of infections  
Table 7-2: Commercially available molecular diagnostics for sepsis  
Table 7-3: FDA-approved molecular diagnostics for various bacterial infections 
Table 7-4: Commercially available molecular diagnostics for fungal infections  
Table 7-5: FDA-approved molecular diagnostics for viral infections 
Table 7-6: Companies with molecular diagnostics for influenza virus H1N
Table 7-7: Companies with molecular diagnostics for avian influenza virus H5N
Table 7-8: COVID-19 diagnostic pipeline
Table 7-9: Commercially available molecular diagnostics for C. difficile
Table 7-10: Companies developing POC tests for the diagnosis of infections 
Table 7-11: Selected companies involved in molecular diagnosis of infections  
Table 8-1: Estimated new cases of cancer in the US of most involved organs - 
Table 8-2: Tumor suppressor genes, their chromosomal location, function, and associated tumors 
Table 8-3: Viruses linked to human cancer 
Table 8-4: A classification of molecular diagnostic methods in cancer  
Table 8-5: Desirable characteristics of biomarkers for cancer 
Table 8-6: Approved monoclonal antibodies for cancer diagnosis  
Table 8-7: Methods for comparison of gene-expression profiling in tumor specimens 
Table 8-8: Companies that have important cancer tests based on gene signatures 
Table 8-9: Companies developing technologies for detection of CTCs  
Table 8-10: Impact of in vivo molecular imaging of cancer on oncology practice  
Table 8-11: Molecular diagnostic tests for breast cancer  
Table 8-12: Companies developing cancer molecular diagnostics  
Table 9-1: Applications of molecular diagnostics in the biopharmaceutical industry 
Table 9-2: Molecular diagnostic technologies for drug discovery 
Table 9-3: Molecular diagnostic technologies used for pharmacogenetic studies
Table 9-4: Companies with novel molecular toxicology technologies 
Table 9-5: Applications of molecular diagnostics in gene therapy  
Table 9-6: Companies involved in transplant molecular diagnostics  
Table 9-7: Companies involved in molecular diagnostics of blood transfusions  
Table 9-8: Pathogenic bacteria in food and targets for molecular diagnostic probes
Table 9-9: Companies involved in molecular diagnostics for food-borne infections  
Table 9-10: Testing for harmful prions in brain tissue from dead cattle 
Table 9-11: Companies involved in developing molecular diagnostics for TSEs 
Table 9-12: Companies involved in detection of genetically modified food  
Table 9-13: Companies involved in companion diagnostics 
Table 9-14: Applications of point-of-care diagnosis 
Table 9-15: Companies developing point-of-care diagnostic tests 
Table 10-1: Forensic and legal applications of molecular diagnostics.  
Table 10-2: Molecular technologies used for forensic applications 
Table 10-3: Biological and chemical agents used as weapons of mass destruction
Table 10-4: Biological warfare agents that can be identified by PCR methods 
Table 10-5: Companies developing devices for detection of biological warfare agents 

Figures

Figure 1-1: Extrachromosomal DNA  
Figure 1-2: Relation of molecular diagnostics to other technologies 
Figure 2-1: PlexZyme technology for PlexPCR 
Figure 2-2: Rolling circle amplification technology
Figure 2-3: A schematic view of the Invader operating system 
Figure 2-4: Principle of fluorescent in situ hybridization  
Figure 2-5: Repli-G system of QIAGEN  
Figure 2-6: DNA sequencing process  
Figure 2-7: Electrochemical detection of DNA  
Figure 2-8: Elements of a Scorpions primer 
Figure 3-1: Affymetrix GeneChip technology 
Figure 3-2: Basic principle of a biosensor 
Figure 3-3: Surface plasmon resonance (SPR) technology
Figure 7-1: Use of DNA chips in diagnosing microbial infections 
Figure 7-2: High throughput DNA pyrosequencing for pathogen discovery 
Figure 9-1: The mechanism of SHERLOCK for POC diagnosis  

Part II: Regulations, Markets & Companies

12. Ethics, Patents and Regulatory issues  

• Introduction 
• Ethical concerns about genetic diagnosis
• Ethical guidelines for molecular diagnostics  
• Ethical aspects of use of WGS for newborn and prenatal screening 
• Ethical aspects of direct-to-consumer genetic services  
• US public attitudes about genetic testing 
• Opinion of European geneticists about DTC genetic testing
• Genetic testing for susceptibility to adult-onset cancer  
• Ethics of preimplantation genetic diagnosis 
• Preimplantation genetic diagnosis to screen for hereditary diseases 
• PGD to test for susceptibiliy to cancer
• PGD and stem cells 
• Genetic research on stored tissues 
• Informed consent in clinical trials of in vitro devices 
• Concluding remarks about ethical issues 
• Insurance underwriting and gene tests 
• Should genetic information be available to health insurers? 
• A need for the re-examination of current views 
• Genetic Information Nondiscrimination Act of US  
• Impact of the US health care reform bill on genetic testing issues 
• Patents for molecular diagnostics
• PCR patents 
• Patenting DNA sequences 
• US policy on gene patenting relevant to molecular diagnostics
• The impact of disease gene patents on molecular diagnostics  
• Licensing problems associated with genetic testing 
• BRCA1 and BRCA2 gene patents 
• Role of the WHO in genetic testing standards 
• NIH's Genetic Testing Registry 
• Regulatory issues in the US 
• Assay Migration Studies for In Vitro Diagnostic Devices 
• Assessment of diagnostic accuracy
• Sensitivity and specificity  
• Documentation of diagnostic accuracy  
• Discovery of incidental findings on genetic screening  
• Evaluation of companion diagnostics/therapeutic for cancer 
• FDA regulation of multivariate index assays  
• FDA guidance for IVDs to detect pathogens
• FDA guidelines for devices to detect and differentiate HPV 
• FDA's Microarray Quality Control
• FDA and point-of-care diagnosis 
• Genetic testing of rare disorders 
• Guidelines for developing omics-based tests 
• Shared responsibility on oversight of omics-based tests 
• Guidelines for use of sequencing for molecular diagnosis  
• FDA oversight of next generation sequencing 
• Quality control of molecular diagnostic laboratory procedures  
• Quality assurance of RNA expression profiling
• Quality control of point-of-care tests 
• Regulation of IVD by the FDA 
• FDA guidance on research use and investigational use only IVDs 
• Regulation of in vitro companion diagnostics by the FDA
• Regulation of in vivo diagnostics by the FDA 
• Regulation of laboratory developed tests
• Home-brew tests 
• Laboratory-developed tests used by Medicare recipients 
• Oversight of LDTs by the FDA  
• Alternative to FDA LDT guidance 
• Regulatory aspects of FISH 
• Regulation of genetic testing  
• Role of the FDA in genetic testing  
• Regulation of direct-to-consumer genetic testing 
• Need for regulatory oversight of DTC
• Regulatory issues concerning blood and plasma products 
• United States Diagnostics Standards 
• Regulation of in vitro diagnostics in the EU 
• EU regulations for testing of blood products  
• Regulation of genetic testing in EU 
• Evaluation of diagnostic laboratory tests in the UK  
• Pre-implantation genetic diagnosis in the UK 

13. Markets for Molecular Diagnostics  

• Introduction 
• Methods for study of molecular diagnostic markets
• The overall market for diagnostic technologies 
• Markets for in vitro diagnostics  
• Molecular diagnostic markets according to technologies 
• Marketing strategies according to technologies 
• Nucleic acid isolation market  
• Market for PCR-based tests 
• Markets for PCR instrumentation
• Markets for real-time PCR and qRT-PCR 
• PCR market players
• DNA sequencing market
• Cost of NGS 
• Cytogenetic market 
• Market for FISH technologies
• Biochip/microarray market  
• Biosensor market
• Nanobiotechnology for molecular diagnostics
• Markets for gene expression technologies  
• Reagents and other disposable laboratory materials 
• Market for immunochemistry diagnostic 
• Markets for tissue diagnostics
• Molecular diagnostic markets according to therapeutic areas 
• Genetic disorders 
• Prenatal testing  
• Non-invasive prenatal testing  
• Cancer
• Potential markets for cancer diagnosis according to type of cancer  
• Infectious diseases
• Diagnostics for COVID-19 
• Sexually transmitted diseases 
• Hospital-acquired infections 
• Testing for HIV drug resistance
• Potential markets for avian influenza diagnostics  
• Cardiovascular diseases 
• Neurological disorders  
• Food testing 
• Screening of blood for transfusion 
• Tissue typing for transplantation 
• Molecular diagnostic markets relevant to pharmaceutical industry 
• Molecular diagnosis and personalized medicine markets
• Growth of markets relevant to personalized medicine 
• Point-of-care market  
• Marketing opportunities according to geographic areas 
• Unmet needs in molecular diagnostics
• Major market trends 
• Markets according to home-brew and FDA-approved tests 
• Decentralization of molecular diagnostics 
• Direct-to-consumers healthcare testing  
• Point-of-care testing 
• Development of personalized medicine 
• Cost of sequencing the human genome
• Cost of genotyping  
• Marketing companion diagnostics for personalized medicine  
• Development of low-cost tests
• Simplification of test procedures 
• Increasing role of proteomics in clinical diagnostics 
• Forensic and legal applications  
• Veterinary molecular diagnostics
• Marketing strategies 
• Role of alliances in commercialization of molecular diagnostics 
• Acquisitions vs collaborations  
• Analysis of collaborations in molecular diagnostics 
• Licensing of the technologies 
• Strategies related to laboratory facilities and technologies 
• Strategies relevant to the healthcare system 
• Cost-Benefit studies 
• Genetic susceptibility testing 
• Preventive medicine strategies 
• Targeting treatable and common diseases
• Information/education  
• Physician education
• Patient education 
• European diagnostic information platform 
• Regulatory strategies 
• Merger of in vitro and in vivo diagnostics 
• Integration of diagnostics with therapeutics  
• Diagnostic applications in clinical trials 
• Prospects for development of new technologies 
• Drivers for the development of molecular diagnostics 
• Factors slowing the development of molecular diagnostics 
• Cost of sequencing the human genome  
• Challenges and future prospects for diagnostic applications of sequencing  
• US organizations for advancing molecular diagnostic industry 
• AdvaMedDx 
• European projects for improving molecular diagnostics  
• European Consortium for developing new DNA analysis tools
• EU project for improvement of IVD tools procedures 
• Genetic knowledge parks in the UK 
• Molecular diagnostic opportunities in defense against bioterrorism 
• Molecular diagnostics for food safety 
• POC diagnostics for the Asian countries  

14. Companies involved in molecular diagnostics 

• Introduction 
• Major players in molecular diagnostics 
• Profiles of selected companies
• Collaborations

Tables

Table 13-1: Share of in vitro diagnostics in the global diagnostic market 2020-2030 
Table 13-2: Molecular diagnostics markets according to technologies from 2020-2030 
Table 13-3: PCR market 2020-2030  
Table 13-4: Molecular diagnostics markets according to applications 2020-2030
Table 13-5: Markets in 2020 for tests to screen healthy persons for genetic disorders  
Table 13-6: Markets in 2020 for molecular diagnostic screening tests for cancer
Table 13-7: Molecular diagnostic markets for selected cancers 2020-2030 
Table 13-8: Markets value in 2020 for molecular diagnostic screening for infections 
Table 13-9: Future markets for HAI diagnostics 2020-2030  
Table 13-10: Growth of markets relevant to personalized medicine 2020-2030  
Table 13-11: Molecular diagnostic markets according to geographical areas 2020-2030  
Table 13-12: Molecular diagnostic markets according to home-brew and approved tests 
Table 13-13: Marketing strategies for molecular diagnostics 
Table 13-14: Acquisitions of molecular diagnostic companies 
Table 13-15: Advantages of the integration of diagnostics with therapeutics 
Table 14-1: Top ten players in molecular diagnostics  
Table 14-2: Collaborations of companies in molecular diagnostics 

Figures

Figure 13-1: Unmet needs in applications of molecular diagnostics 

Samples