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Nanotechnology  Creation of useful materials, devices, and systems through the manipulation of matter on nanometer scale. - Generally nanotechnology deals.

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Presentation on theme: "Nanotechnology  Creation of useful materials, devices, and systems through the manipulation of matter on nanometer scale. - Generally nanotechnology deals."— Presentation transcript:

1 Nanotechnology  Creation of useful materials, devices, and systems through the manipulation of matter on nanometer scale. - Generally nanotechnology deals with structures sized between 1 to 100 nanometer in at least one dimension.  Ability to design systems with defined structure and function on the nanometer scale.  Involves developing materials, devices within that size, and analytical tools (methodology), which can be used for analysis and measurement on a molecular scale  Interdisciplinary area : Biology, Physics, Chemistry, Material science, Electronics, Chemical Engineering, Information technology

2 Nanotechnology Plays by Different Rules Normal scaleNanoscale

3 Analytical methods and Nano-sized materials  Analytical tools : Atomic force microscopy(AFM), Electron microscopy (EM)  Nano-sized materials  Unusual and different property - Semiconductor nanocrystals: Size-dependent optical property - N anoparticles: Magnetic nanoparticles (F erromagnetic, superparamagnetic), Gold, Carbon nanotubes, Quantum dots (Semiconductor nanocrystals)

4 Future implications of nanotech  Nanotechnology may be able to create many new materials and devices with a vast range of applications, such as in medicine, biomaterials, electronics, and energy production.  Nanotechnology raises many of the same issues as with any introduction of new technology, including concerns about the toxicity and environmental impact of nanomaterials, and their potential effects on global economics.

5 Nano-Biotechnology  Integration of nano-sized/structured materials, nano-scale analytical tools, and nano-devices into biological sciences for development of new biomaterials and analytical toolkits as well as for understanding life science  Use of bio-inspired molecules or materials  Typical characteristics of Biological events/materials - Self assembly - Highly efficient : high energy yield - Very specific : extremely precis e  Bio-molecules Proteins, DNA, RNA, Aptamers, Peptides, Antibody, Virus

6 Nano-Bio Convergence Molecular Switch DNA barcode Molecular Imaging Biochip / Biosensor Nanotherapy / Delivery Bio-TechnologyNano-Technol Bionano-machine / Nano-Robot Bio-inspired device and system

7 Applications and Perspectives of Nanobiotechnology  Development of tools and methods - More sensitive - More specific - Multiplexed - More efficient and economic  Implementation  Diagnosis and treatment of diseases - Rapid and sensitive detection (Biomarkers, Imaging) - Targeted delivery of therapeutics  Drug development - Understanding of life science

8 Examples  Nano-Biodevices  Nano-Biosensors  Imaging with nanoparticles  Analysis of a single molecule/ a single cell

9 Issues to be considered  Synthesis or selection of nano-sized/ structured materials  Functionalization with biomolecules or for biocompatibility  Integration with devices and/or analytical tools  Assessment : Reproducibility, Toxicity  Implementation

10 The size of Things

11 NanoBiotech was initiated by the development of AFM that enables imaging at atomic level in 1980

12 AFM (Atomic Force Microscope)  A cantilever with a sharp tip (probe) at its end that is used to scan the specimen surface  When the top is brought into a close proximity of a sample surface, force between the tip and sample leads to a deflection of the cantilever according to Hooke’s law  Deflection is measured using a laser spot reflected from the top surface of the cantilever into an array of photodiode One of the foremost tools for imaging, measuring, and manipulating matters at the nanoscale.

13 VEECO TESPA ® VEECO TESPA-HAR ® NANOWORLD SuperSharpSilicon ® Tip length : 10  m Radius : 15~20 nm Tip length :10  m (last 2  m 7:1) Radius : 4~10 nm Tip length :10  m Radius : 2 nm

14 Example showing the resolution of protein structure by AFM Image of ATP synthase composed of 14subunits

15 Molecular imaging  Biomedical & Biological Sciences :  Ultra-sensitive imaging of biological targets under non-invasive in-vivo conditions  Fluorescence, positron emission tomography, Magnetic resonance imaging  Ultra-sensitive imaging - Cancer detection, cell migration, gene expression, localization of proteins, angiogenesis, apotosis - MRI : P owerful imaging tool as a result of non-invasive nature, high spatial resolution and tomographic capability Resolution is highly dependent on the molecular imaging agents  Signal enhancement by using contrast agents : iron oxide nanoparticles

16 - Properties and Biological Applications Semiconductor Nanocrystals Quantum Dots

17 Synthesis of CdSe/ZnS (Core/Shell) QDs Step 1 CdO + Se CdSe Step 2 ZnEt 2 + S(TMS) 2 CdSe ZnS Solvent : TOPO, HAD, TOP Surfactant : TDPA, dioctylamine Growth temperature  140 ℃ (green) 200 ℃ (red) 320 ℃ CdO solution Se solution Thermocouple 20 nm CdSe/ZnS 5.5 nm (red) Bawendi et al. J. Am. Chem. Soc. (1994)

18 Optical Properties Of Quantum Dots a) Multiple colors b) Photostability c) Wide absorption and narrow emission d) High quantum yield Quantum Yield ≥ 60 ~ 70 % Single source excitation

19 QD Surface Coating for Biocompatibility ① CdSe/ZnS core-shell Quantum Dots Encapsulated in Phospholipid Micelles CdSe QDs Dubertret et al. Science (2002) PEG-PE (n-poly(ethylenglycol)phosphatidylethanolamine): micell-forming hydrophilic polymer-grafted lipids  comparable to natural lipoproteins PEG : low immunogenic and antigenic, low non-specific protein binding PC : Phosphatidylcholine Encapsulation with the hydrophobic core of a micell Coating with PC Coating of the outer shell with ZnS

20 QD Y Y Y Y Y Y Y Y Organelle + QD-Antibody conjugates Antigen QD Y Y Y Y Y Y Y Y Organelle ▲ 3T3 cell nucleus stained with red QDs and microtubules with green QDs In Vivo Cell Imaging Wu et al. Nature Biotech. 2003 21 41 - Multiple Color Imaging - Stronger Signals - Multiple Color Imaging - Stronger Signals

21 In Vivo Cell Imaging Quantum Dot Injection ▶ Red Quantum Dot locating a tumor in a live mouse Live Cell Imaging Cell Motility Imaging 10um ◀ Green QD filled vesicles move toward to nucleus (yellow arrow) in breast tumor cell Alivisatos et al., Adv. Mater., 2002 14 882

22 Inherent capabilities of molecular recognition and self-assembly Attractive template for constructing and organizing the nano-structures Proteins, toxin, coat proteins of virus etc. Biosystems

23 α -Hemolysin: Self-Assembling Transmembrane Pore  A self-assembling bacterial exo-toxin produced by some pathogens like Staphylococcus aureus as a way to obtain nutrients  lysis of red blood cells  Alpha-hemolysin monomers bind to the outer membrane of susceptible cells.  Monomers oligomerize to form a water-filled heptameric transmembrane channel that facilitates uncontrolled permeation of water, ions, and small organic molecules.  Rapid discharge of vital molecules, such as ATP, dissipation of the membrane potential and ionic gradients, and irreversible osmotic swelling leading to the cell wall rupture (lysis), can cause death of the host cell.

24 - Mushroom-like shape with a 50 A beta-barrel stem - Narrowest part (1.4 nm in diameter) of channel at the base of stem

25 - Magnitude of the current reduction : type of analyte - Frequency of current reduction intervals: analyte concentration  A molecular adaptor is placed inside its engineered stem, influencing the transmembrane ionic current induced by an applied voltage  Reversible binding of analytes to the molecular adaptor transiently reduces the ionic current Biotechnological applications :Stochastic sensors

26 Stochastic Sensors

27 a : Histidine captured metal ions (Zn+2, Co+2, mixture ) b: CD captures anions (promethazine, imipramine, mixture) c : biotin ligand

28 DNA sequencing  Transmembrane pore can conduct big (tens of kDa) linear macromolecules like DNA or RNA  Eelectrophoretically-driven translocation of a 58-nucleotide DNA strand through the transmembrane pore of alpha-hemolysin  Changes in the ionic current by the chemical structure of individual strands  Nucleotide sequence directly from a DNA or RNA strand  A single nucleotide resolution

29 Understanding Cancer and Related Topics Understanding Nanodevices Developed by: Jennifer Michalowski, M.S. Donna Kerrigan, M.S. Jeanne Kelly Brian Hollen Explains nanotechnology and its potential to improve cancer detection, diagnosis, and treatment. Illustrates several nanotechnology tools in development, including nanopores, quantum dots, and dendrimers. These PowerPoint slides are not locked files. You can mix and match slides from different tutorials as you prepare your own lectures. In the Notes section, you will find explanations of the graphics. The art in this tutorial is copyrighted and may not be reused for commercial gain. Please do not remove the NCI logo or the copyright mark from any slide. These tutorials may be copied only if they are distributed free of charge for educational purposes.

30 What Is NanoBiotechnology? Nanodevices Nanopores Dendrimers Nanotubes Quantum dots Nanoshells Tennis ballA periodWhite blood cell Water molecule

31 Designing Nanodevices for Use in the Body Too BigToo Small

32 Manufacturing Nanodevices Scattered X-rays Atoms in crystal Detector NanodevicesCrystalWhite blood cell CrystalX-ray beam

33 Nanodevices Are Small Enough to Enter Cells Cell White blood cell Water molecule Nanodevices

34 Nanodevices Can Improve Cancer Detection and Diagnosis ImagingNanoBiotechnologyPhysical Exam, Symptoms

35 Nanodevices Can Improve Sensitivity and determine which cells are cancerous or precancerous. Precancerous cells Normal cells Nanodevices could potentially enter cells Precancerous cells Normal cells

36 Nanodevices Can Preserve Patients’ Samples Cells from patient Cells preserved Active state preserved Cells altered Active state lost Additional tests Cells from patient Nanotechnology Tests Traditional Tests

37 Nanodevices Can Make Cancer Tests Faster and More Efficient Patient APatient B

38 Cantilevers Can Make Cancer Tests Faster and More Efficient Cancer cell Water molecule Nanodevices Cantilevers Antibodies with proteins Antibodies White blood cell Bent cantilever

39 Nanopores A Single- stranded DNA molecule Single-stranded DNA molecule White blood cell Water molecule Nanodevices Nanopores Single-stranded DNA molecule ATCGATCG Nanopore T

40 Quantum Dots Ultraviolet light off White blood cell Water molecule Nanodevices Quantum dots Quantum dots emit light Ultraviolet light on Quantum dots Quantum dot bead

41 Quantum Dots Can Find Cancer Signatures Cancer cells Healthy cells Quantum dot beads Healthy cells Cancer cells

42 Improving Cancer Treatment Nanotechnology TreatmentTraditional Treatment Intact noncancerous cells Noncancerous cells Toxins Nanodevices Cancer cells Dead noncancerous cells Noncancerous cells Drugs Dead cancer cells Dead cancer cells Toxins Cancer cells

43 Nanoshells Nanoshell White blood cell Water molecule Nanodevices Nanoshells Gold Near-infrared light onNear-infrared light off Nanoshell absorbs heat

44 Nanoshells as Cancer Therapy Nanoshells Dead cancer cells Nanoshells Cancer cells Healthy cells Intact healthy cells Near-infrared light Healthy cells Cancer cells

45 Nanodevices as a Link Between Detection, Diagnosis, and Treatment Nanodevice Reporting TargetingDetection Imaging NanoBiotechnology Cancer Treatment Cancer cell Traditional Cancer Treatment Cancer cell Drug

46 Dendrimers Dendrimer White blood cell Water molecule Nanodevices Dendrimer Cancer cell

47 Dendrimers : Highly Branched Dendritic Macromolecules

48 ● Characteristics  Monodisperse macromolecule  Globular (Spherical)  Facile surface bio-functionalization  Similar molecular size to biomolecules (Glucose oxidase 6  5.2  7.7 nm) Molecular carriers for chemical catalysts (Core, Peripheral) Medical applications (MRI contrast enhancer) Biomimetic catalysts (Peptides-, Glycodendrimers) Vehicles for delivery of genes and drugs Poly (amido amine) Dendrimers 4.5 nm G4 Poly(amidoamine) Dendrimer ● Applications

49 Dendrimers as Cancer Therapy Cell death monitor Reporter Therapeutic agent Cancer detector Water molecule White blood cell Nanodevices Dendrimer Manipulate dendrimers to release their contents only in the presence of certain trigger (molecules or light)  caged molecules

50 NanoBiotechnologies in Patient Care Today2020

51 We would like to hear from you... If you have questions about this tutorial’s content, suggestions for new topics, or other feedback on the Web site, please send an e-mail to kerrigad@mail.nih.gov. If you have questions about this tutorial’s artwork or want permission to use it, please send an e-mail to beankelly@verizon.net.


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