Nanobiotechnologies - applications, markets and companies

0. Executive Summary  17

1. Basics of Nanobiotechnology ....... 19

Introduction 19

Classification of nanobiotechnologies . 20

Top-down and bottom-up approaches...21

Landmarks in the evolution of nanobiotechnology... 21

Relation of nanobiotechnology to healthcare ........... 22

2. Technologies........... 25

Introduction 25

Micro- and nano-electromechanical systems............ 25

BioMEMS...25

Microarrays and nanoarrays................ 26

Dip Pen Nanolithography for nanoarrays ..26

Protein nanoarrays ...........27

Microfluidics and nanofluidics ............. 28

Nanotechnology on a chip .28

Microfluidic chips for nanoliter volumes .29

Nanogen's NanoChip.........30

Use of nanotechnology in microfluidics..31

Construction of nanofluidic channels 31

Nanoscale flow visualization ...........32

Moving (levitation) of nanofluidic drops with physical forces ......32

Electrochemical nanofluid injection ..32

Nanofluidics on nanopatterned surfaces ................33

Nano-interface in a microfluidic chip 33

Nanofluidic channels for study of DNA.33

Visualization and manipulation on nanoscale........... 34

Atomic force microscopy ...34

Basic AFM operation ....34

Advantages of AFM......34

Force sensing Integrated Readout and Active Tip ...35

Ultra-nanocrystalline diamond .............35

Magnetic resonance force microscopy ...36

Scanning probe microscopy .................36

Near-field scanning optical microscopy..36

Nano-sized light source for single cell endoscopy ........37

Multiple single-molecule fluorescence microscopy........37

Nanoparticle characterization by HaloÔ LM10 technology ...............37

Nanoscale scanning electron microscopy ..38

Use of SEM to reconstruct three-dimensional tissue nanostructure 39

Visualizing atoms with scanning electron microscopy ................39

Photoactivated localization microscopy39

Optical Imaging with a Silver Superlens 40

Fluorescence Resonance Energy Transfer .40

4Pi microscope.................40

Principle and applications of cantilevers 41

Companies that provide microscopes for nanobiotechnology ...........42

Surface plasmon resonance ................ 43

Nanoparticles. 43

Quantum dots44

Gold nanoparticles............45

Silica nanoparticles...........45

Lipoparticles ..45

Assembly of nanoparticles into micelles 46

Biomedical applications of self-assembly of nanoparticles ...............46

Paramagnetic and superparamagnetic nanoparticles....47

Fluorescent nanoparticles..48

Production techniques for nanoparticles 48

Nanostructures ................. 49

Bacterial structures relevant to nanobiotechnology ......49

Bacterial spores ..........49

Nanostructures based on bacterial cell surface layers................49

Bacterial magnetic particles............50

Cubosomes 50

Dendrimers 51

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Properties 52

Applications................52

DNA-nanoparticle conjugates...............53

DNA octahedron...............53

Potential applications ...53

Fullerenes ..53

Nanoshells .54

Nanotubes.55

Carbon nanotubes .......55

Carbon nanotubes and DNA............56

Applications of nanotubes...............56

Nanobuds..57

Nanowires ..57

Nanostamping .................57

Nanoneedles..58

Nanopores.58

Nanoporous silica aerogel..59

Nanostructured silicon ......60

Networks of gold nanoparticles and bacteriophage ......60

Polymer nanofibers...........60

Protein-nanoparticle combination .........60

Nanomaterials for biolabeling ............. 61

Quantum dots as labels.....62

Silver nanoparticle labels ..63

Silica nanoparticles for labeling antibodies63

SERS nanotags ................63

DNA Nanotags .................64

Fluorescent lanthanide nanorods ..........64

Organic nanoparticles as biolabels........64

Molecular computational identification...65

Companies providing services and products for nanobiotechnology ............... 65

3. Applications in Life Sciences........ 67

Introduction 67

Nanotechnology and biology ............... 67

NanoSystems Biology .......67

Nanobiology and the cell ...68

Measuring mass of single cells ........69

Nanotechnology-based live-cell single molecule assays .............69

Quantum dots for cell labeling ........69

Quantum dots for study of apoptosis ..70

Single cell injection by nanolasers ...70

Nanostructures involved in endocytosis.................70

Study of complex biological systems71

Biosensing of cellular responses ......71

Control of T cell signaling activity ....72

Molecular motors .............72

Nanomotor made of nucleic acids ....74

phi29 DNA packaging nanomotor ....74

Light-activated ion channel molecular machines.....75

Application of AFM for biomolecular imaging ...............75

Future insights into biomolecular processes by AFM76

4Pi microscopy to study DNA double-strand breaks .....76

Multi-isotope imaging mass spectrometry.77

Applications of biomolecular computing in life sciences 77

Molecular electronics ........78

Microbial nanomaterials ....78

Use of bacteria to construct nanomachines ............78

Bacteriophage nanoshells ...............78

Natural nanocomposites....79

Nanotechnology in biological research...79

Nanoparticles for biological research79

Disguising quantum dots as proteins for cell entry..80

Molecular biology and nanotechnology ..81

DNA nanotechnology ...81

Reversibly binding of gold nanospheres to DNA strands.............82

RNA nanotechnology....82

Genetically engineered proteins for nanobiotechnology .............83

Single molecule studies.....83

Optical trapping and single-molecule fluorescence..83

3D single-molecular imaging by coherent X-ray diffraction imaging .................84

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Studying the molecular mechanisms of enzymes....84

Nanochemistry 84

Nanoscale pH Meter..........85

Application of nanolasers in life sciences................. 85

Nanomanipulation............. 85

Nanomanipulation by combination of AFM and other devices...........86

Surgery on living cells using AFM with nanoneedles.....86

Optoelectronic tweezers....86

Nanomanipulation of single molecule ....87

Fluorescence-force spectroscopy ..........87

Nanomanipulation for study of mechanism of anticancer drugs .......88

Nanotechnology in genomic research . 88

Use of nanotechnology for separation of DNA fragments ................88

Nanotechnology-based DNA sequencing88

Single-molecule detection of DNA hybridization...........89

Role of nanobiotechnology in identifying single nucleotide polymorphisms.............89

Nanobiotechnology for study of mitochondria.......... 90

Nanomaterials for the study of mitochondria...............90

Study of mitochondria with nanolaser spectroscopy.....90

Role of nanotechnology in proteomics research....... 91

Study of proteins by atomic force microscopy .............91

Single cell nanoprobe for studying gene expression of individual cells .91

Nanoproteomics...............91

Multi Photon Detection.92

Nanoflow liquid chromatography .....92

High-field asymmetric waveform ion mobility mass spectrometry ..92

Protein nanocrystallography ...........93

QD-protein bioconjugate nanoassembly ................93

Nanoproteomics for study of misfolded proteins .....93

Dynamic reassembly of peptides .....94

Use of nanotube electronic biosensor in proteomics 94

Nanometer photomasks from bacterial protein.......94

Proteomics at single molecule level ......95

Study of protein synthesis and single-molecule processes .........95

Protein expression in individual cells at the single molecule level96

Single-molecule mass spectrometry using a nanopore ..............96

Biochips for nanoscale proteomics ........97

Protein biochips based on fluorescence planar wave guide technology..............97

Nanofilter array chip ....97

Role of nanotechnology in study of membrane proteins98

Nanoparticles for study of membrane proteins .......98

Study of single protein interaction with cell membrane .............98

Quantum dots to label cell surface proteins ...........98

Study of single membrane proteins at subnanometer resolution.99

Nanoparticle-protein interactions..........99

Protein engineering on nanoscale .........99

Nanowires for protein engineering ...99

A nanoscale mechanism for protein engineering... 100

Role of nanoparticles in self-assembly of proteins. 100

Role of nanotechnology in peptide engineering..... 100

Manipulating redox systems for nanotechnology. ...... 101

Self-assembling peptide scaffold technology for 3-D cell culture.... 101

Nanobiotechnology and ion channels 102

Aquaporin water channels ................. 102

Role of nanobiotechnology in engineering ion channels ................ 103

Application of nanobiotechnology in molecular electronics...... 104

Nanotechnology and bioinformatics.. 104

3D nano-map of synapse  105

Companies providing nanotechnology for life sciences research. 105

4. Nanomolecular Diagnostics ....... 107

Introduction. 107

Nanodiagnostics.............. 107

Rationale of nanotechnology for molecular diagnostics................. 108

Nanoarrays for molecular diagnostics.. 109

NanoPro™ System.......... 109

Nanofluidic/nanoarray devices to detect a single molecule of DNA . 109

Self-assembling protein nanoarrays.... 110

Fullerene photodetectors for chemiluminescence detection on microfluidic chip.... 110

Protein microarray for detection of molecules with nanoparticles ... 110

Protein nanobiochip ........ 111

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Nanoparticles for molecular diagnostics ................ 111

Gold nanoparticles.......... 111

Quantum dots for molecular diagnostics. 112

Quantum dots for detection of pathogenic microorganisms ...... 113

Bioconjugated QDs for multiplexed profiling of biomarkers ...... 113

Imaging of living tissue with quantum dots.......... 113

Magnetic nanoparticles ... 114

Magnetic nanoparticles for bioscreening .............. 114

Superparamagnetic nanoparticles for cell tracking  114

Monitoring of implanted NSCs labeled with nanoparticles......... 115

Perfluorocarbon nanoparticles to track therapeutic cells in vivo  115

Superparamagnetic iron oxide nanoparticles for calcium sensing . 115

Magnetic nanoparticles for labeling molecules ...... 115

Ferrofluids ................ 116

Super conducting quantum interference device .... 116

Study of living cells by superparamagnetic nanoparticles......... 116

Use of nanocrystals in immunohistochemistry........... 117

Imaging applications of nanoparticles . 117

Gadonanotubes for MRI ............... 117

Gold nanorods and nanoparticles as imaging agents ............... 118

In vivo imaging using nanoparticles.. 118

Manganese oxide nanoparticles as contrast agent for brain MRI .. 118

Nanoparticles vs microparticles for cellular imaging ................ 119

Nanoparticles as contrast agent for MRI .............. 119

Quantum dots for biological imaging. 119

Superparamagnetic nanoparticles combined with MRI............. 120

Study of chromosomes by atomic force microscopy................. 121

Applications of nanopore technology for molecular diagnostics.. 121

DNA-protein and -nanoparticle conjugates ............ 122

Resonance Light Scattering technology ................. 123

DNA nanomachines for molecular diagnostics........ 123

Nanobarcodes technology................. 124

Nanobarcode particle technology for SNP genotyping. 124

Qdot nanobarcode for multiplexed gene expression profiling......... 124

Biobarcode assay for proteins ............ 125

Single-molecule barcoding system for DNA analysis... 126

Nanoparticle-based colorimetric DNA detection method .......... 127

SNP genotyping with gold nanoparticle probes .......... 127

Nanoparticle-based Up-converting Phosphor Technology ........ 128

Surface-Enhanced Resonant Raman Spectroscopy. 128

Near-infrared (NIR)-emissive polymersomes ........ 129

Nanobiotechnology for detection of proteins ......... 129

Captamers with proximity extension assay for proteins................ 129

Nanobiosensors .............. 129

Cantilevers as biosensors for molecular diagnostics ... 130

Advantages of cantilever technology for molecular recognition. 131

Antibody-coated nanocantilevers for detection of microorganisms ................. 131

Cantilevers for direct detection of active genes .... 132

Portable nanocantilever system for diagnosis....... 132

Carbon nanotube biosensors.............. 132

Carbon nanotube sensors coated with ssDNA and electronic readout ............. 133

Carbon nanotubes sensors wrapped with DNA and optical detection .............. 133

FRET-based DNA nanosensor............. 133

Ion Channel Switch biosensor technology ................. 134

Electronic nanobiosensors ................. 134

Electrochemical nanobiosensor........... 135

Quartz nanobalance biosensor ........... 135

Viral nanosensor ............ 135

PEBBLE nanosensors ...... 136

Nanosensors for glucose monitoring ... 136

Microneedle-mounted biosensor......... 137

Optical biosensors .......... 137

Laser nanosensors..... 137

Nanoshell biosensors . 138

Plasmonics and SERS nanoprobes . 138

Novel optical mRNA biosensor....... 138

Optonanogen biosensor ............... 139

Surface plasmon resonance technology............... 140

Surface Enhanced Micro-optical Fluidic Systems... 140

Nanowire biosensors....... 141

Nanowire biosensors for detection of single viruses ................ 141

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Nanowires for detection of genetic disorders........ 142

Nanowires biosensor for detecting biowarfare agents.............. 142

Concluding remarks and future prospects of nanowire biosensors 142

Nanoscale erasable biodetectors ........ 143

Future issues in the development of nanobiosensors.. 143

Applications of nanodiagnostics........ 144

Nanotechnology for detection of biomarkers ............. 144

Nanotechnology for genotyping of single-nucleotide polymorphisms . 145

Nanoparticles for detecting SNPs... 145

Nanopores for detecting SNPs....... 145

Nanobiotechnologies for single molecule detection .... 146

Protease-activated quantum dot probes . 147

Labeling of MSCs with QDs ................ 147

Nanotechnology for detection of cancer.. 147

QDs for cancer diagnosis.............. 148

Dendrimers for sensing cancer cell apoptosis ....... 148

Nanoparticles designed for dual-mode imaging of cancer......... 149

Gold nanoparticles for cancer diagnosis............... 149

Gold nanorods for detection of metastatic tumor cells ............. 150

Nanoatomic tubes for detection of cancer proteins 150

Nanodots for tracking apoptosis in cancer ........... 151

Nanoparticles for the optical imaging of tumors.... 151

Nanolaser spectroscopy for detection of