Abstract
Benefits of this report
- This report has evolved during the past ten years, profiting from feedback by numerous readers and experts.
- The most comprehensive and up-to-date one-stop source of information on technical and commercial aspects of molecular diagnostics.
- Includes profiles of 250 companies, the largest number in any report on this topic.
- 450 references, cited in the report are included in the bibliography.
- The text is supplemented by 83 tables and 13 figures.
Who should read this report?
- Chief executive officers of molecular diagnostic companies.
- Business development executives of pharmaceutical and biotechnology companies.
- Executives of companies involved in developing integration of diagnosis and treatment as well as those interested in personalized medicine.
- Officers of genomic and proteomic companies interested in diagnostic technologies.
- Research scientists involved in application of molecular diagnostic technologies.
- Planners of healthcare services.
Summary
This report describes and evaluates the molecular diagnostics technologies that will play an important role in practice of medicine, public health, pharmaceutical industry, forensics and biological warfare in the 21st century. This includes several polymerase chain reaction (PCR)-based technologies, fluorescent in situ hybridization (FISH), peptide nucleic acids (PNA), electrochemical detection of DNA, biochips, nanotechnology and proteomic technologies.
Initial applications of molecular diagnostics were mostly for infections but are now increasing in the areas of genetic disorders, preimplantation screening and cancer. Genetic screening tests, despite some restrictions is a promising area for future expansion of in vitro diagnostic market. Molecular diagnostics is being combined with therapeutics and forms an important component of integrated healthcare. Molecular diagnostic technologies are also involved in development of personalized medicine based on pharmacogenetics and pharmacogenomics. Currently, there has been a considerable interest in developing rapid diagnostic methods for for point-of-care and biowarfare agents such as anthrax.
The number of companies involved in molecular diagnostics has increased remarkably during the past few years. More than 500 companies have been identified to be involved in developing molecular diagnostics and 250 of these are profiled in the report along with tabulation of 573 collaborations. Despite the strict regulation, most of the development in molecular diagnostics has taken place in the United States, which has the largest number of companies.
The markets for molecular diagnostics technologies are difficult to estimate. Molecular diagnostics markets overlap with markets for non-molecular diagnostic technologies in the in vitro diagnostic market and are less well defined than those for pharmaceuticals. Molecular diagnostic markets are analyzed for 2007 according to technologies, applications and geographical regions. Forecasts are made up to 2017. A major portion of the molecular diagnostic market can be attributed to advances in genomics and proteomics. Biochip and nanobiotechnology are expected to make a significant contribution to the growth of molecular diagnostics.
This report was first published as DNA Diagnostics in 1995 by PJB Publications, UK. It was updated in 1997 as Molecular Diagnostics and the next edition, Molecular Diagnostics II, was published by Decision Resources Inc in 1999. All the three versions of the reports were well accepted and sold widely.The report has been rewritten several times since then.
Table of Contents
0. Executive Summary
1. Introduction
- Definitions and scope of the subject
- Historical evolution of molecular diagnostics
- Molecular biology relevant to molecular diagnostics
- Genome
- DNA
- DNA polymerases
- Restriction endonucleases
- DNA methylation
- RNA
- RNA polymerases
- Chromosomes
- Telomeres
- Mitochondrial DNA
- Genes
- The genetic code
- Gene expression
- DNA sequences
- Junk DNA
- Single nucleotide polymorphisms
- Genotype and haplotypes
- Replication of the DNA helix
- 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
- Limitations of PCR
- Impact of human genome project on molecular diagnostics
- Genetic variations in the human genome
- Insertions and deletions in the human genome
- Large scale variation in human genome
- Variation in copy number in the human genome
- Structural variations in the human genome
- Mapping and sequencing of structural variation from human genomes
- 1000 Genomes Project
- Genetic variations in the human genome
- Biomarkers
- Applications of molecular diagnostics
2. Molecular Diagnostic Technologies
- Introduction
- DNA extraction
- Transrenal DNA
- Sample preparation
- 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 that are suitable for automation
- Xtra Amp Genomic DNA Extraction
- Extraction of DNA from paraffin sections
- Dynabead technology
- Pressure Cycling Technology
- SamPrep
- Use of magnetic particles for automation in genome analysis
- Companies involved in nucleic acid isolation
- Novel PCR methods
- Real-time PCR systems
- Dyes used in real-time PCR
- Commercially available real-time PCR systems
- LightCycler PCR system
- LightUp probes based on real-time PCR
- Applications of real-time PCR
- Limitations of real-time PCR
- Improving the reliability of low level DNA analysis by real-time PCR
- Future applications of real-time Q-PCR
- Reverse transcriptase (RT)-PCR
- Standardized reverse transcriptase PCR
- Single cell PCR
- LATE-PCR
- AmpliGrid-System
- Digital PCR
- Combined PCR-ELISA
- Real-time PCR systems
- Monitoring of gene amplification in molecular diagnostics
- Non-PCR nucleic acid amplification methods
- Linked Linear Amplification
- Transcription mediated amplification
- Rapid analysis of gene expression
- WAVE nucleic acid fragment analysis system
- DNA probes with conjugated minor groove binder
- Rolling circle amplification technology
- Gene-based diagnostics through RCAT
- RCAT-immunodiagnostics
- RCAT-biochips
- RCAT-pharmacogenomics
- Circle-to-circle amplification
- Ramification amplification method
- Single Primer Isothermal Amplification
- Isothermal reaction for amplification of oligonucleotides
- ICAN (Isothermal and Chimeric primer-initiated Amplification of Nucleic Acids)
- 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 Amplification Technology
- Direct molecular analysis without amplification
- Direct detection of dsDNA
- Multiplex assays
- Fluorescent in situ hybridization
- 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
- Automation of FISH
- Companies involved in FISH diagnostics
- RNA diagnostics
- Branched-chain DNA assay for measurement of RNA
- Cycling probe technology
- Linear RNA amplification
- Solid Phase Transcription Chain Reaction
- Nucleic acid sequence-based amplification
- Q Beta replicase system
- Non-isotopic RNase cleavage assay
- Invader RNA assays
- Visualization of mRNA expression in vivo
- Whole genome amplification
- Companies that provide technologies for whole genome amplification
- QIAGEN' s Repli-G system
- GenomePlex™ - Whole Genome Amplification
- Companies that provide technologies for whole genome amplification
- DNA sequencing
- Sanger-sequencing technology
- Enhancements of Sanger-sequencing
- Limitations of Sanger-sequencing technology
- Emerging sequencing technologies
- Cyclic array sequencing
- 454 Pyrosequencing technology
- Electron microscope-based DNA sequencing
- Illumina Genome Analyzer System
- Multiplex amplification of human DNA sequences
- Sequential DEXAS
- Sequencing by hybridization
- SOLiD technology
- Whole genome sequencing
- Bioinformatic tools for analysis of genomic sequencing data
- Detection of single molecules in real time
- Direct observation of nucleotide incorporation
- Molecular Combing
- Nanopore sequencing
- DNA sequence by use of nanoparticles
- Future prospects of sequencing
- Sanger-sequencing technology
- Genome-wide approach for chromatin mapping
- Mitochondrial sequencing
- Identification of unknown DNA sequences
- Optical mapping
- Gene expression analysis
- MAUI (MicroArray User Interface) hybridization
- Ziplex™ system
- Serial analysis of gene expression (SAGE)
- Tangerine™ expression profiling
- Analysis of single-cell gene expression
- Gene expression profiling based on alternative RNA splicing
- Whole genome expression array
- T cell receptor expression analysis
- Monitoring in vivo gene expression by molecular imaging
- Gene expression profiling on whole blood samples
- Profiling gene expression patterns of white blood cells
- 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
- Electrochemical detection of DNA
- Mediated nucleic acid oxidation
- Detection of hybridized nucleic acid with cyclic voltametry
- Electrochemical detection based on Toshiba' s CMOS technology
- Concluding remarks on electrochemical DNA detection
- Scorpions™ technology
- The Scorpions reaction
- Applications of Scorpion
3. Biochips, Biosenors, and Molecular Labels
- Introduction to biochip technology
- Applications of biochips in diagnostics
- GeneChip
- GeneChip Human Genome Arrays
- AmpliChip CYP450
- Electronic detection of nucleic acids on microarrays
- Strand displacement amplification on a biochip
- Rolling circle amplification on DNA microarrays
- 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
- GeneChip
- Microfluidic chips
- Fish-on-chip
- Lab-on-a-chip
- LabCD
- Micronics' microfluidic technology
- Microfluidic automated DNA analysis using PCR
- Microfluidic chips integrated with PET
- OptiChip™
- Companies developing microfluidic technologies
- Biosensor technologies
- Classification of biosensor technologies
- DNA-based biosensors
- DNA hybridization biosensor chips
- PCR-free DNA biosensor
- 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
- Microsensors using with nano/microelectronic communications technology
- Electrochemical sensors
- Enzyme electrodes for biosensing
- Conductometric sensors
- Electrochemical genosensors
- Electrochemical nanobiosensor
- Bioelectronic sensors
- Phototransistor biochip biosensor
- Ribozyme-based sensors
- RiboReporters
- Concluding remarks and future prospects of biosensor technology
- Companies developing biosensors for molecular diagnostics
- Molecular labels and detection
- Detection technologies for molecular labels
- Fluorescence and chemiluminescence
- 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
- Molecular imaging
- Companies involved in molecular imaging
- Challenges and future prospects of molecular imaging
- Basic research in molecular imaging
- Devices for molecular imaging
- Molecular imaging in clinical practice
- Protein-DNA chimeras for detection of small numbers of molecules
- Single-molecule detection
- Atomic force microscopy
- Capillary electrophoresis
- Confocal laser scanning
- Spectrally resolved fluorescence lifetime imaging microscopy
- Nanobiotechnology for molecular diagnostics
- Magnetic nanoparticles
- Gold nanoparticles
- Quantum dot technology
- Nanotechnology on a chip
- Nanogen' s NanoChip
- Fullerene photodetectors for chemiluminescence detection on microfluidic chip
- Diagnostics based on nanopore technology
- Nanosensors
- Quartz nanobalance biosensor
- PEBBLE nanosensors
- Nanosensors for glucose monitoring
- Cantilever arrays
- Resonance Light Scattering technology
- DNA nanomachines for molecular diagnostics
- Nanobarcodes technology for molecular diagnostics
- Qdot nanobarcode for multiplexed gene expression profiling
- Role of nanobiotechnology in improving molecular diagnostics
- Companies involved in nanomolecular diagnostics
- Concluding remarks about nanodiagnostics
- Future prospects 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
- Diagnostics based on designed repeat proteins
- Differential Peptide Display
- Light-switching excimer probes
- MALDI-TOF Mass Spectrometry
- Molecular beacon aptamer
- Molecular beacon assay
- Proteomic patterns
- Biomarkers of disease
- 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
- Protein biochips based on fluorescence planar wave guide technology
- 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 prospects 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
- SignatureChipR-based diagnostics for cytogenetic abnormalities
- 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
- 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
- Mutation detection technologies
- Technologies for SNP analysis
- DNA sequencing
- Electrochemical DNA probes
- Use of NanoChip for detection of SNPs
- Single base extension-tag array
- Laboratory Multiple Analyte Profile
- SNP genotyping with gold nanoparticle probes
- PCR-CTPP (confronting two-pair primers)
- Peptide nucleic acid probes for SNP detection
- SNP genotyping on a genome-wide amplified DOP-PCR template
- Pyrosequencing
- Reversed enzyme activity DNA interrogation test
- Smart amplification process version 2
- Zinc finger proteins
- UCAN method (Takara Biomedical)
- 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
- OmniScan SNP genotyping
- Affymetrix SNP genotyping array
- Concluding remarks on SNP genotyping
- Limitations of SNP in genetic testing
- Haplotyping versus SNP genotyping
- Determination of copy number variations
- Companies involved in developing technologies/products for SNP analysis
- Prenatal DNA diagnosis
- Amniocentesis
- Chorionic villus sampling
- Biochip for separating fetal cells for genetic diagnosis
- Antenatal screening for Down' s syndrome
- Fetal cells in maternal blood
- Molecular methods for prenatal diagnosis
- PCR for prenatal diagnosis
- FISH for prenatal diagnosis
- In vivo gene expression analysis of the living human fetus
- Applications of prenatal diagnosis
- Diagnosis of congenital infections
- Diagnosis of eclampsia
- Use of transrenal DNA for prenatal testing
- Preimplantation genetic diagnosis
- Technologies for preimplantation genetic diagnosis (PGD)
- PCR for preimplantation genetic diagnosis
- FISH for preimplantation genetic diagnosis
- Microarrays for preimplantation genetic diagnosis
- Conditions detected by preimplantation genetic diagnosis
- The future of preimplantation genetic diagnosis
- Technologies for preimplantation genetic diagnosis (PGD)
- Companies involved in prenatal/preimplantation diagnosis
- Cystic fibrosis
- Detection of CFTR gene mutations
- CFTR technologies of various companies
- Genzyme' s CF gene sequencing
- CF Plus™ - Tag-It Cystic Fibrosis Kit
- Asuragen' s bead array test
- The Ambry CF Test
- Biochip for CF diagnosis
- MassARRAY® system for high-throughput CFTR testing
- 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
- Hemoglobinopathies
- Polycystic kidney disease
- Hereditary metabolic disorders
- Lesch-Nyhan Syndrome
- Gaucher' s Disease
- Acute Intermittent Porphyria
- Phenylketonuria
- Hereditary periodic fever
- Achondroplasia
- Molecular diagnosis of cardiovascular disorders
- Coronary Heart Disease
- Cardiomyopathy
- Familial Hypertrophic Cardiomyopathy
- Idiopathic dilated cardiomyopathy
- 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
- 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
- Parkinson' s disease
- Spinal muscular atrophy
- Duchenne and Becker muscular dystrophy
- Triple repeat disorders
- Huntington disease
- Fragile X syndrome
- Charcot-Marie Tooth disease
- Hereditary neuropathy with liability to pressure palsies
- eNOS gene polymorphisms as predictor of cerebral aneurysm rupture
- Mitochondrial disorders affecting the nervous system
- Genetic testing for disease predisposition
- Personal genetic service
6. Molecular Diagnosis of Infections
- Introduction
- Molecular techniques for the diagnosis of infections
- Antibody-enhanced microplate hybridization assays
- Biosensors for detection of microorganisms
- Ibis T5000™ Biosensor System
- 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
- LightCycler SeptiFast Test
- Ligase chain reaction
- Metagenomic pyrosequencing
- Multiplex PCR for detection of infections
- Dual priming oligonucleotide for multiplex PCR
- Nucleic acid probes
- Neutrophil CD11b expression as a diagnostic marker
- PNA-FISH for 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
- 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 and fungal infections
- Mycobacterium tuberculosis
- Conventional diagnosis of tuberculosis
- Microscopic Observation Drug Susceptible Assay for tuberculosis
- Molecular diagnostics for tuberculosis
- Combined tuberculin testing and ELISpot PLUS assay
- Biomarkers for tuberculosis
- Diagnosis of drug-resistant M. tuberculosis infection
- Cost-effectiveness of PCR in tuberculosis screening
- Other mycobacteria
- Chlamydial infections
- Neisseria gonorrhoeae
- Bacteria associated with bacterial vaginosis
- Group B Streptococci
- Pseudomonas aeruginosa
- Helicobacter pylori
- Lyme disease
- Mycoplasmas
- Fungal infections
- Mycobacterium tuberculosis
- Viral infections
- HIV/AIDS
- Diagnosis of HIV
- Neonatal screening of infants of HIV-positive mothers
- Screening of cadaveric tissue donors
- Detection of HIV provirus
- Resolution of indeterminate Western blot
- Global Surveillance of HIV-1 genetic variations
- Genotyping for drug-resistance in HIV
- Phenotyping as predictor of drug susceptibility/resistance in HIV
- Tests used for quantification of HIV
- Conclusions about HIV genotyping
- 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
- 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
- West Nile and St. Louis encephalitis viruses
- HIV/AIDS
- Protozoal infections
- Amebiasis
- Cryptosporidium parvum
- 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
- SARS-associated coronavirus
- Influenza viruses
- Avian influenza
- Gastrointestinal infections
- Periodontal infections
- Diagnosis of urinary infections by a biosensor
- Rapid testing in septicemia
- CNS infections
- Role of molecular diagnostics in resistance to antimicrobial drugs
- Bacterial genome sequencing in antimicrobial resistance
- Molecular diagnostics and Human Microbiome Project
- Concluding remarks and future prospects of diagnosis of infections
- Rapid point-of-care diagnosis of infection
- Diagnosis of viruses using protein fingerprinting
- QIAplex PCR multiplex technology
- Companies involved in molecular diagnosis of infectious diseases
7. Molecular Diagnosis of Cancer
- Introduction
- Cancer Genetics
- Oncogenes
- Tumor Suppressor Genes
- p53
- p16
- Viruses and cancer
- Conventional cancer diagnosis
- Molecular techniques for cancer diagnosis
- Genome analysis at the molecular level
- Mutation detection at molecular level
- Expression profiling of tumor cells sorted by flow cytometry
- MicroRNA expression profiling to classify human cancers
- Biomarkers in cancer
- eTag assay system for cancer biomarkers
- HAAH as a biomarker for cancer
- Methods for detection of DNA methylation
- Circulating nucleosomes in serum of cancer patients
- LigAmp for detection of gene mutations in cancer
- Mitochondrial DNA as a cancer biomarker
- 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
- Monoclonal antibodies for diagnosis of cancer
- 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
- Measurement of telomerase activity
- Survivin and molecular diagnosis of cancer
- Detection of cancer cells in blood of patients with solid tumors
- Epithelial aggregate separation and isolation
- DNA tags for finding genes expressed in cancer
- Oncoproteins as biomarkers for cancer
- HER-2/neu oncoprotein
- Proteomic technologies for the molecular diagnosis of cancer
- Laser capture microdissection in oncology
- Proteomic technologies for tumor markers
- Automated image analysis of nuclear protein distribution
- Affibodies as contrast agents for imaging in cancer
- Layered expression scanning
- Aptamer-based technology for protein signatures of cancer cells
- Aptamers for combined diagnosis and therapeutics of cancer
- Biochip/microarrays for cancer diagnosis
- Role of DNA microarrays in gene expression profiling
- Biochip detection of FHIT gene
- Nanotechnology for early detection of cancer
- Quantum dots for early detection of cancer
- Magnetic nanoparticle probes
- Detection of nanoparticle self assembly in tumors by MRI
- Molecular imaging of cancer
- PET for in vivo molecular diagnosis of cancer
- Xenon-enhanced MRI
- Optical systems for in vivo molecular imaging of cancer
- Recombinant antibodies as a novel approach to cancer diagnosis
- Detection of micrometastases
- Molecular diagnosis of cancers of various organs
- Brain tumors
- Molecular diagnostic methods for brain tumors
- Glioblastoma multiforme
- Combination of neuroimaging and DNA microarray analysis in GBM
- Medulloblastoma
- Oligodendroglioma
- Advantages and limitations of molecular diagnosis of brain tumors
- Breast cancer
- Breast cancer genes
- Molecular diagnostic tests for breast cancer
- Mouse ESC-based assays to evaluate mutations in BRCA2
- Genomic profiles of breast cancer
- Role of molecular diagnostics in management of breast cancer
- Tests for prognosis of breast cancer
- Prediction of recurrence in breast cancer for personalizing therapy
- Cervical cancer
- Colorectal cancer
- Diagnosis of hereditary nonpolyposis colorectal cancer
- Detection of familial adenomatous polyposis coli
- Diagnosis of colorectal cancer from DNA in stools
- Detection of circulating tumor cells in colorectal cancer
- Minimally invasive screening for colorectal cancer
- Guanylyl cyclase C tests for colorectal cancer
- Head and neck cancer
- Hematological malignancies
- Chromosome translocations
- Flow cytometry in diagnosis of leukemia
- Gene chip technology
- Laboratory assessment of leukemia
- Molecular probes
- Minimal residual disease
- Screening of gene mutations in chronic myeloproliferative diseases
- Lung cancer
- 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
- Prostate cancer
- Gene expression analysis of prostate cancer by microarrays
- Huntingtin Interacting Protein 1
- Integrative genomic and proteomic profiling of prostate cancer
- LCM for diagnosis of prostate cancer
- PCA3 gene detection in urine
- PCR assay for assessing silencing of protein cadherin 13 gene
- Prostate biopsy for detection of prostatic intraepithelial neoplasia
- Screening of multiple SNPs for risk of prostate cancer
- Semen testing for prostate cancer biomarkers
- Serum-protein fingerprinting in prostate cancer
- Thyroid cancer
- 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
- Brain tumors
- 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
- Personalized therapy for cancer patients
- Pharmacogenetics and cancer therapy
- Molecular diagnostics as an aid to selection of cancer therapy
- Drug resistance in cancer
- Role of organizatons in molecular diagnosis of cancer
- Role of NCI in molecular diagnosis of cancer
- Molecular profiling of cancer
- Cancer Genome Atlas
- Cancer Genetic Markers of Susceptibility Project
- Role of the International Cancer Genome Consortium
- Role of NCI in molecular diagnosis of cancer
- Future prospects of molecular diagnosis of cancer
- Companies involved in molecular diagnosis of cancer
8. 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
- Toxicogenomics
- Toxicoproteomics
- Mitochondrial assays
- MetaChip
- Molecular diagnostics and pharmacogenomics
- Applications molecular diagnostics in gene therapy
- Use of PCR to study biodistribution of gene therapy vector
- 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
- Detection of microbial contamination in biopharmaceutical manufacturing
- Role of PCR in detecting contamination of biopharmaceuticals
- Contamination of biopharmaceuticals with prions
- DNA tagging for control and tracing of drug distribution channels
- Molecular diagnostics for organ transplantation
- Tissue typing
- Commercial products for transplant diagnostics
- Post-cardiac transplant patient monitoring for rejection
- Blood Transfusion Screening
- 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
- PRISMR automated system
- Procleix HIV-1/HCV Assay
- West Nile virus detection in human blood
- Limitations of molecular diagnostics for blood screening
- Molecular epidemiology
- Molecular epidemiology of genetic diseases
- 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 epidemiology of genetic diseases
- 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
- Optical biosensor for detection of Listeria-contaminated foods
- Companies with technologies for food pathogen detection
- Transmissible spongiform encephalopathies (TSEs)
- Molecular diagnosis of TSEs
- Companies involved in developing molecular diagnostics for TSEs
- Detection of genetically modified organisms in 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
- Companies combining diagnostics and therapeutics
- Point-of-care diagnosis
- Technologies for point-of-care diagnosis
- Biochips for point-of-care diagnosis
- Companies developing point-of-care diagnosis
- Point-of-care diagnosis of infections
- Advantages versus disadvantages of point-of-care diagnosis
- The impact of molecular diagnostics on clinical laboratory practice
9. Molecular Diagnostics in Forensic Medicine and Biological Warfare
- Application of molecular diagnostics in forensic medicine
- Technologies
- Extraction of DNA from forensic samples
- Mitochondrial DNA (mtDNA) analysis
- Polymorphic Alu insertions
- Single Nucleotide Polymorphisms (SNP) analysis
- Short tandem repeat (STR)
- Fluorescent detection systems
- ABO genotyping
- 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
- Technologies
- 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
- Commercial development of diagnostic devices for biological agents
- Companies developing diagnostic devices for biological agents
- Biodefence microarray
- Identification of genetic markers of individual pathogens
- Microbial Identification System based on OptiChip™
- Hand-Held Advanced Nucleic Acid Analyzer
- Nanogen' s portable detection device
- Nanode Array Sensor Microchips
- MicroChemLab
- BioThreat Alert Test Strip
- Benchtop living cell biosensor
- BioForce NanoArray sensor technology
- QTL handheld biosensor
- Analyte 2000 biosensor
- Airborne bacterial spore detection technology
- Destruction and detection of anthrax by lysin
- Biosensor based on mass spectrometry of microorganisms' s RNA
- Bead ARray Counter
- ProteinChip-based detection of bioterroism agents
- TIGER biosensor
- The PathAlert™ - Detection System
- Concluding remarks about biodefense applications of diagnostics
10. 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: Some commercially available real-time PCR systems
- Table 2 - 3: Applications of real-time PCR
- 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: Comparison of methods of identification of unknown DNA sequences
- Table 2 - 8: Classification of methods of gene expression analysis
- Table 2 - 9: A selection of companies with gene expression technologies
- Table 2 - 10: Companies involved in developing PNA 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: Companies involved in developing 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: Genes that cause cardiovascular diseases
- Table 5 - 9: Available molecular diagnostics for neurogenetic diseases
- Table 5 - 10: Companies offering genetic screening tests directly to consumers
- Table 6 - 1: Molecular techniques for the diagnosis of infections
- Table 6 - 2: Bacteria and fungi that can be detected by recombinant DNA tests
- Table 6 - 3: Viruses that can be detected by recombinant DNA methods
- Table 6 - 4: Companies with molecular diagnostics for avian influenza virus H5N1
- Table 6 - 5: Selected companies involved in clinical molecular diagnosis of infections
- Table 7 - 1: Estimated new cases of cancer in the US at most involved organs - 2006
- Table 7 - 2: Tumor suppressor genes, their chromosomal location, function, and associated tumors
- Table 7 - 3: Viruses linked to human cancer
- Table 7 - 4: A classification of molecular diagnostic methods in cancer
- Table 7 - 5: Desirable characteristics of biomarkers for cancer
- Table 7 - 6: Approved monoclonal antibodies for cancer diagnosis
- Table 7 - 7: Methods for comparison of gene-expression profilling in tumor specimens
- Table 7 - 8: Impact of in vivo molecular imaging of cancer on oncology practice
- Table 7 - 9: Companies developing cancer molecular diagnostics
- Table 8 - 1: Applications of molecular diagnostics in the biopharmaceutical industry
- Table 8 - 2: Molecular diagnostic technologies for drug discovery
- Table 8 - 3: Molecular diagnostic technologies used for pharmacogenetic studies
- Table 8 - 4: Companies with novel molecular toxicology technologies
- Table 8 - 5: Applications of molecular diagnostics in gene therapy
- Table 8 - 6: Companies involved in molecular diagnostics of blood transfusions
- Table 8 - 7: Pathogenic bacteria in food and targets for molecular diagnostic probes
- Table 8 - 8: Companies involved in molecular diagnostics for food-borne infections
- Table 8 - 9: Testing for harmful prions in brain tissue from dead cattle
- Table 8 - 10: Companies involved in developing molecular diagnostics for TSEs
- Table 8 - 11: Companies combining molecular diagnostics and therapeutics
- Table 8 - 12: Applications of point-of-care diagnosis
- Table 8 - 13: Companies developing point-of-care diagnostic tests
- Table 9 - 1: Forensic and legal applications of molecular diagnostics
- Table 9 - 2: Molecular technologies used for forensic applications
- Table 9 - 3: Classification of biological and chemical agents used as weapons of mass destruction
- Table 9 - 4: Biological warfare agents that can be identified by PCR methods
- Table 9 - 5: Companies developing detection devices for biological warfare agents
Figures
- Figure 1 - 1: Relation of molecular diagnostics to other technologies
- Figure 2 - 1: Rolling circle amplification technology
- Figure 2 - 2: A schematic view of the Invader operating system
- Figure 2 - 3: Principle of fluorescent in situ hybridization
- Figure 2 - 4: Repli-G system of Qiagen
- Figure 2 - 5: Electrochemical detection of DNA
- Figure 2 - 6: 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 6 - 1: Use of DNA chips in diagnosing microbial infections
- Figure 6 - 2: High throughput DNA pyrosequencing for pathogen discovery
11. Ethics, Patents and Regulatory issues
- Introduction
- Ethical concerns about genetic diagnosis
- Ethical guidelines for molecular diagnostics
- Ethical and regulatory aspects of direct-to-consumer genetic services
- 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
- Patents for molecular diagnostics
- PCR patents
- Patenting DNA sequences
- The impact of disease gene patents on molecular diagnostics
- Licensing problems associated with genetic testing
- Evaluation of diagnostic laboratory tests in the UK
- Regulatory issues
- Regulation of IVD by the FDA
- FDA guidance for IVDs to detect pathogens
- Regulation of in vivo diagnostics by the FDA
- Regulation of analytic-specific reagents
- Regulatory aspects of FISH
- FDA' s Microarray Quality Control
- Regulation of genetic testing
- Role of the FDA in genetic testing
- Regulation of genetic testing in Europe
- Pre-implantation genetic diagnosis in the UK
- Role of the WHO in genetic testing standards
- Genetic testing of rare disorders
- Quality control of molecular diagnostic laboratory procedures
- Assessment of diagnostic accuracy
- Sensitivity and specificity
- Documentation of diagnostic accuracy
- Discovery of incidental findings on genetic screening
- Regulatory issues concerning blood and plasma products
- Quality control of point-of-care tests
- FDA and point-of-care diagnosis
- Evaluation of companion diagnostics/therapeutic for cancer
- FDA regulation of multivariate index assays
- Regulation of in vitro diagnostics in the EU
12. Markets for Molecular Diagnostics
- Introduction
- Methods for study of molecular diagnostic markets
- The overall market for diagnostic technologies
- Molecular diagnostic markets according to technologies
- Marketing strategies according to technologies
- Nucleic acid isolation market
- Market for PCR-based tests
- DNA sequencing market
- 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
- Cancer
- Potential markets for cancer diagnosis according to type of cancer
- Infectious Diseases
- Potential markets for avian influenza diagnostics
- Cardiovascular diseases
- Food testing
- Screening of blood for transfusion
- Tissue typing for transplantation
- Marketing opportunities according to geographic areas
- Unmet needs in molecular diagnostics
- Major market trends
- Point-of-Care testing
- Development of personalized medicine
- Cost of sequencing the human genome
- Cost of genotyping
- Development of low-cost tests
- Simplification of test procedures
- Increasing role of proteomics in clinical diagnostics
- Forensic and legal applications
- 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
- Government support of research relevant to molecular diagnostics
- Cost of sequencing the human genome
- Genetic knowledge parks in the UK
- Molecular diagnostic opportunities in defense against bioterrorism
- Molecular diagnostics for food safety
- Molecular diagnostics for hospital acquired infections
- POC diagnostics for the developing countries
13. Companies involved in molecular diagnostics
- Introduction
- Major players in molecular diagnostics
- Profiles of selected companies
- Collaborations
Tables
- Table 12 - 1: Share of in vitro diagnostics in the global diagnostic market 2007-2017
- Table 12 - 2: Molecular diagnostics markets according to technologies from 2007-2017
- Table 12 - 3: Molecular diagnostics markets according to applications 2007-2017
- Table 12 - 4: Markets in 2007 for tests to screen healthy persons for genetic disorders
- Table 12 - 5: Markets in 2007 for molecular diagnostic tests for cancer
- Table 12 - 6: Molecular diagnostic markets for selected cancers 2007-2017
- Table 12 - 7: Markets value in 2007 for molecular diagnostic screening for infections
- Table 12 - 8: Molecular diagnostic markets according to geographical areas 2007-2017
- Table 12 - 9: Marketing strategies for molecular diagnostics
- Table 12 - 10: Takeovers of molecular diagnostic companies
- Table 12 - 11: Advantages of the integration of diagnostics with therapeutics
- Table 13 - 1: Top ten players in molecular diagnostics
- Table 13 - 2: Collaborations of companies in molecular diagnostics
Figures
- Figure - 12 1: Unmet needs in applications of molecular diagnostics
- Figure - 12 2: Proportion of various areas in molecular diagnostic collaborations
