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Quantum Dots.pdf

  1. Quantum Dots
  3. • Nanoparticles are particles that have dimension of 100 nm or less in size. • The properties of many conventional materials change when formed from nanoparticles. • This is typically because nanoparticles have a greater surface area per weight than larger particles; this causes them to be more reactive to certain other molecules.
  4. • Iron nanoparticles are used to clean up carbon tetrachloride pollution in ground water. • Designed by Oregon Health & Science University's OGI School of Science & Engineering, in collaboration with Pacific Northwest National Laboratory (PNNL) and the University of Minnesota.
  5. • Carbon tetrachloride is a manufactured toxic chemical used mainly in cleaning fluids and degreasing agents. • Spillage infiltrates the soil and creates very large areas of contaminated groundwater and soil in few areas causing cancer in animals. • A commercially available product of iron oxide with a magnetite shell high in sulfur, quickly and effectively degraded carbon tetrachloride to a mixture of relatively harmless products.
  6. • Researchers at MIT and Harvard Medical School have built targeted nanoparticles that can cling to artery walls and slowly release medicine, an advance that potentially provides an alternative to drug-releasing stents in some patients with cardiovascular disease.
  7. • The particles, dubbed “nanoburrs” ,are coated with tiny protein fragments that allow them to stick to target proteins. • They are designed to release their drug payload over several days and are one of the first such targeted particles that can precisely home in on damaged vascular tissue.
  9. INTRODUCTION • Quantum dots are tiny particles,or “nanoparticles”, of a semiconductor material, traditionally chalcogenides (selenides or sulfides) of metals like cadmium or zinc (CdSe or ZnS), which range from 2 to 10 nanometers in diameter (about the width of 50 atoms).
  10. • They are the smallest objects that can be synthesized on the nanoscale. • Like the name suggests, its structure is much like a small dot. Common shapes include pyramids, cylinders, lens shapes, and spheres. • Different synthesis routes create different kinds of quantum dots.
  11. • Quantum dots are so important because they confine electrons in three dimensions. • The reason 'quantum' prefixes the name is because the dots exhibit quantum confinement properties in all three dimensions i.e. electrons within a dot can't freely move around in any direction.
  12. • The ability to precisely control the size of a quantum dot enables the manufacturer to determine the wavelength of the emission, which in turn determines the colour of light the human eye perceives. • Quantum dots exhibit quantized energy levels like an atom. For a given input energy, for instance, a quantum dot will only emit specific spectra of light. • With decreasing diameters of quantum dots, there is a corresponding increase in energy of emitted light.
  13. • Quantum dots can therefore be “tuned” during production to emit any colour of light desired. The ability to control, or “tune” the emission from the quantum dot by changing its core size is called the “size quantisation effect”. • Due to excellent confinement properties not seen in nanowires or quantum wells (in all modern lasers), quantum dots are extremely efficient at emitting light.
  14. HISTORY • In the 1970s the first low dimensional structures QW (Quantum Wells) were developed. • 1D ( Quantum Wires) and 0D (Quantum Dots) were subsequently developed.
  15. PROPERTIES OF QUANTUM DOTS • Being smaller than the wavelength of the visible light, they cannot be seen under normal conditions. • Quantum Dots luminesce under ultraviolet light, with the size of the dots controlling its colour. • A quantum dot can have anything from a single electron to a collection of several thousands electrons. • Quantum Dots fluoresce or stay lit much longer then dyes conventionally used for tagging cells. • They can be tagged to proteins and their glow enables the identification of specific proteins or DNA making it possible to diagnose various diseases.
  16. The electrons in quantum dots are confined in a small space (quantum box), and when the radii of the semiconductor nanocrystal is smaller than the exciton Bohr radius (exciton Bohr radius is the average distance between the electron in the conduction band and the hole it leaves behind in the valence band), there is quantization of the energy levels according to Pauli’s exclusion principle. The discrete, quantized energy levels of quantum dots relate them more closely to atoms than bulk materials and have resulted in quantum dots being nicknamed 'artificial atoms'. As the size of the crystal decreases, the difference in energy between the highest valence band and the lowest conduction band increases. More energy is then needed to excite the dot, and more energy is released when the crystal returns to its ground state, resulting in a color shift from red to blue in the emitted light. As a result of this phenomenon, quantum dots can emit any color of light from the same material simply by changing the dot size. Additionally, because of the high level of control possible over the size of the nanocrystals produced, quantum dots can be tuned during manufacturing to emit any color of light. Quantum dots have a unique electronic structure
  17. Quantum dots can be classified into different types based on their composition and structure. Core-Type Quantum Dots Quantum dots can be single component materials with uniform internal compositions, such as chalcogenides (selenides or sulfides) of metals like cadmium or zinc, example, CdSe. The photo- and electroluminescence properties of core-type nanocrystals can be fine-tuned by simply changing the crystallite size. Core-Shell Quantum Dots The luminescent properties of quantum dots arise from recombination of electron-hole pairs (exciton decay) through radiative pathways. However, the exciton decay can also occur through nonradiative methods, reducing the fluorescence quantum yield. To improve efficiency and brightness of semiconductor nanocrystals a new method is growing shells of another higher band gap semiconducting material around them. These quantum dots with small regions of one material embedded in another with a wider band gap are known as core-shell quantum dots (CSQDs) or core-shell semiconducting nanocrystals (CSSNCs).
  18. For example, quantum dots with CdSe in the core and ZnS in the shell exhibit greater than 80% quantum yield. Coating quantum dots with shells improves quantum yield by passivizing nonradiative recombination sites and also makes them more robust to processing conditions for various applications. This method has been widely explored as a way to adjust the photophysical properties of quantum dots. Alloyed Quantum Dots Tuning the properties by changing crystallite size could cause problems in many applications with size restrictions. Multicomponent quantum dots is an alternative method to tune properties without changing crystallite size. Alloyed semiconductor quantum dots with both homogeneous and gradient internal structures allow tuning of optical and electronic properties by merely changing the composition and internal structure without changing the crystallite size. For example, alloyed quantum dots of the compositions CdSxSe1-x/ZnS of 6nm diameter emits light of different wavelengths by just changing the composition. Alloyed semiconductor quantum dots formed by alloying together two semiconductors with different band gap energies exhibited interesting properties distinct not only from the properties of their bulk counterparts but also from those of their parent semiconductors. Thus, alloyed nanocrystals possess novel and additional composition-tunable properties aside from properties due to quantum confinement effects.
  19. Visible spectrum • 5 nm dots: red • 1.5 nm dots: violet
  20. Quantum dots change color with size because additional energy is required to “confine” the semiconductor excitation To a smaller volume Ordinary light excites all color quantum dots. (Any light source “bluer” than the dot of interest works.)
  21. COLLOIDAL SYNTHESIS • Colloidal semiconductor nanocrystals - synthesized from precursor compounds dissolved in solutions, much like traditional chemical processes. • The synthesis of colloidal quantum dots is based on a three-component system composed of: precursors, organic surfactants, and solvents.
  22. • The precursors transform into monomers on heating to a suitable temperature. • Once the monomers reach a high enough supersaturation level, the nanocrystal growth starts with a nucleation process. • The temperature during the growth process must be high enough to allow for rearrangement and annealing of atoms during the synthesis process while being low enough to promote crystal growth.
  23. FABRICATION • Self-assembled quantum dots are typically between 5 and 50 nm in size, defined by lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in semiconductor heterostructures. • Some quantum dots are small regions of one material buried in another with a larger band gap. These can be core-shell structures, e.g., with CdSe in the core and ZnS in the shell or from special forms of silica called ormosil. • Quantum dots sometimes occur spontaneously in quantum well structures due to monolayer fluctuations in the well's thickness. • This fabrication method has potential for applications in quantum computation. • The main limitations of this method are the cost of fabrication and the lack of control over positioning of individual dots.
  24. VIRAL ASSEMBLY • Lee et al. (2002) reported using genetically engineered M13 bacteriophage viruses to create quantum dot biocomposite structures. • Genetically engineered viruses can recognize specific semiconductor surfaces. • It is also known that liquid crystalline structures of wild- type viruses (Fd, M13, and TMV) are adjustable by controlling the solution concentrations, ionic strength, and the external magnetic field applied to the solutions. Thus, the specific recognition properties of the virus can be used to organize inorganic nanocrystals, forming ordered arrays over the length scale defined by liquid crystal formation.
  25. • Using this information, Lee et al. (2000) were able to create self-assembled, highly oriented, self-supporting films from a phage and ZnS precursor solution. This system allowed them to vary both the length of bacteriophage and the type of inorganic material through genetic modification and selection.
  26. ELECTROCHEMICAL ASSEMBLY • Highly ordered arrays of quantum dots may also be self- assembled by electrochemical techniques. • A template is created by causing an ionic reaction at an electrolyte-metal interface which results in the spontaneous assembly of nanostructures, including quantum dots, onto the metal which is then used as a mask for mesa-etching these nanostructures on a chosen substrate.
  27. BULK MANUFACTURING • Conventional, small-scale quantum dot manufacturing relies on a process called “high temperature dual injection” which is impractical for most commercial applications that require large quantities of quantum dots. • A reproducible method for creating larger quantities of consistent, high-quality quantum dots involves producing nanoparticles from chemical precursors in the presence of a molecular cluster compound under conditions whereby the integrity of the molecular cluster is maintained and acts as a prefabricated seed template. • Individual molecules of a cluster compound act as a seed or nucleation point upon which nanoparticle growth can be initiated. In this way, a high temperature nucleation step is not necessary to initiate nanoparticle growth because suitable nucleation sites are already provided in the system by the molecular clusters. • A significant advantage of this method is that it is highly scalable.
  28. CADMIUM FREE QUANTUM DOTS • For commercial viability, a range of restricted, heavy metal-free quantum dots has been developed showing bright emissions in the visible and near infra-red region of the spectrum and have similar optical properties to those of CdSe quantum dots. • A new type of CFQD can be made from rare earth (RE) doped oxide colloidal phosphor nanoparticles. Unlike semiconductor nanoparticles, excitation was due to UV absorption of host material, which is same for different RE doped materials using same host. • Multiplexing applications can be thus realized. The emission depends on the type of RE, which enables very large stokes shift and is narrower than CdSe QDs. The synthesis is aqueous based, which eliminated issues of water solubility for biological applications.
  29. 31 Applications • Photovoltaic devices: solar cells • QD Solar paint • Biology: biosensors, imaging • Light emitting diodes: LEDs • Quantum computation • Photodetectors • Lasers 31
  30. 32 Solar Cells • Photovoltaic effect: ▫ p-n junction. ▫ Sunlight excites electrons and creates electron-hole pairs. ▫ Electrons concentrate on one side of the cell and holes on the other side. ▫ Connecting the 2 sides creates electricity. 32
  31. 33 Different Generations of Solar Cells • First generation: ▫ Single crystal silicon wafer. ▫ Advantages: high carrier mobility. ▫ Disadvantages: most of photon energy is wasted as heat, expensive. • Second generation: ▫ Thin-film technology. ▫ Advantages: less expensive. ▫ Disadvantages: efficiency lower compared with silicon solar cells. • Third generation: ▫ Nanocrystal solar cells. ▫ Enhance electrical performances of the second generation while maintaining low production costs.
  32. 34 • The quantum dot band gap is tunable and can be used to create intermediate bandgaps. The maximum theoretical efficiency of the solar cell is as high as 63.2% with this method. How Can Quantum Dots Improve the Efficiency?
  33. Cheap quantum dot solar paint • “Sun Believable solar paint,” consists of a yellow or brown paste made of quantum dots. • The scientists experimented with three types of quantum dots: CdS, CdSe, and TiO2, all of which are powder-like, with water and tert butanol as the solvent. • Instead of adding dye to give the paint a desired color, they added colored semiconductor nanocrystals to the solar paint to achieve the desired optical and electronic properties.
  34. Quantum Dot LEDs • Used to produce inexpensive, industrial quality white light. • Marked improvement over traditional LED-phosphor integration by dot’s ability to absorb and emit at any desired wavelength. • Produce white light by intermixing red, green and blue emitting dots homogenously within the phosphor difficult to accomplish with the traditional LED-phosphor set up.
  35. Biolabelling • Multicolor labeling of cells is a powerful technique for visualizing many structures simultaneously, such as cytoskeletal proteins or organelles, and to elucidate intracellular processes. • QDs have been used to label cellular structures both within and external to the cell membrane. They are delivered inside cells via receptor-mediated pathways where specific ligands were attached to QDs to induce cellular uptake, as well as nonspecific endocytosis (ie, pinocytosis) where cells were incubated with a concentrated QD solution.
  36. Bioimaging • Non invasive, real-time in vivo fluorescence imaging requires exciting fluorophores and detecting their emission through tissue which is invariably hindered by scattering and absorption of both the excitation and emission wavelengths. • Using a filtered halogen source and an IR camera, the collection of QDs within tissue was monitored in real-time to identify a region for surgical resection.
  37. PHOTODETECTORS • Photodetectors based on single quantum dots are expected to find uses in opto-electrical interfaces in future quantum computers, where single photons will carry information over long distances and single electrons will be used for computation.
  38. Futuristic applications • Anti counterfeiting applications: inject dots into liquid mixtures, fabrics, polymer matrices, etc. Ability to specifically control absorption and emission spectra to produce unique validation signatures. Almost impossible to mimic with traditional semi-conductors. • Counter-espionage/Defense applications: Integrate quantum dots into dust that tracks enemies. Protection against friendly-fire events. • New research provides evidence for significant differences between new and old red blood cells used for transfusions and could provide a cheap, rapid and effective way to monitor the quality of blood . • Scientists have discover nanoparticles that can disrupt intracellular transport pathways.
  39. Imaging is an important clinical modality used in determining appropriate cancer therapy. x-ray, computed tomography, ultrasound, radionuclide imaging and MRI, : used widely for cancer screening and staging, determining the efficacy of cancer therapy and monitoring recurrence. 2 major limitations 1. do not have sufficient sensitivity to detect small numbers of malignant cells in the primary or metastatic sites. 2. The imaging techniques have not been developed to detect specific cancer cell-surface markers. In many instances, these cell-surface markers might be targets for cancer therapy and might assist in the diagnosis and staging of cancer. Quantum dot (QD) imaging probes, although still in the early development stage, provide the potential to fulfill these requirements for in vivo cancer imaging. QDs In Cancer Therapy
  40. QDs vs Organic Fluorescent dyes QDs offer great advantages over traditional organic fluorescent dyes and present a number of beneficial characteristics for spectroscopy, such as 1. high fluorescence intensity (brightness) 2. long lifetime 3. good resistance to photobleaching. 4. have broad excitation and narrow and symmetric emission spectra, which make it feasible to perform 'multiplexing' (simultaneous detection of multiple signals) imaging using a single excitation source 5. high sensitivity for simultaneous cancer molecular imaging and targeted therapy. the sensitivity of QD-based molecular imaging can be two to three orders larger than that of routine fluorescent dyes. Furthermore, the fluorescence in near infrared of NIR-QDs can be detected in deep tissues, making them suitable for in vivo imaging with high signal-to- background ratio
  41. Biocompatibility of QDs QDs are highly hydrophobic and, therefore, only soluble in organic solvents. Thus often encapsulated by amphiphilic molecules. The hydrophobic segment of these molecules interacts with the hydrophobic molecules on the QD surface, whereas the hydrophilic segment interacts with the aqueous medium, solublizing the QDs. Several types of amphiphilic polymers, including polyethylene glycol (PEG)-derived phospholipids, triblock copolymers, octylamine-modified polyacrylic acid, oligomeric phosphine and copolymers of alkyl monomers and anhydrides, can serve this encapsulation function. After encapsulation, the hydrodynamic radius of QDs increases to 10-20 nm. To functionalize QDs with biomolecules, amphiphilic polymers are engineered to carry reactive groups, such as amines and carboxylic acids. Biomolecules, such as peptides, antibodies, DNA or siRNA, can react with these functional groups to form covalent linkages mediated by various coupling reagents.
  42. In addition, biomolecules can be conjugated with QDs through noncovalent affinity binding, such as the interactions of biotin/avidin, or nickel nitrilotriacetic acid (Ni- NTA)/histidine-tagged peptides. Controlling ratio of reactive groups and reaction time, the average number of biomolecules conjugated to each QD can be controlled average of two or a few biomolecules are typically conjugated to one QD. Encapsulation and bioconjugation do not usually alter the optical property of QDs significantly. Recently, QDs based on silicon have drawn much attention because of their potential lower toxicity than heavy metal QDs, such as Cd/Se dots. Silicon QDs are typically 2-8 nm in size. The surface of QDs can be passivated with organic ligands, such as octadecene and dodecene, resulting in QDs that are more stable during storage with dramatically increased quantum yield and solubility in organic solvents. Some silicon QDs emit fluorescence at red and infrared range, which is ideal for in vivo imaging. However, their excitation wavelength normally lies in the ultraviolet region, which penetrates poorly into tissues and might be damaging to cells.
  43. Detection of primary tumor in vitro Biocompatible QDs were introduced for imaging of cancer cells in vitro in 1998. Researchers have synthesized QD-based probes conjugated with cancer specific ligands, antibodies, or peptides for cancer imaging and diagnosis in vitro. Compared with traditional immunohistochemistry, QD-IHC is more accurate and precise at low protein expression levels and can achieve quantitative detection which will provide much more information for personalized treatment. Prostate cancer Gao et al. labeled human prostate cancer cells based on the conjugate of QDs with an antibody for prostate specific membrane antigen (PSMA). QD-based immunolabelling has more stable photo-intensity compared with conventional fluorescent immunolabelling. Superior quality of QD-IHC compared with conventional IHC has been demonstrated along with simultaneous detection of androgen receptor and PSA in prostate cancer cells based on multiplexing QDs. The detection sensitivity of QD-based prostate cancer biomarkers can be enhanced by surface plasmon-coupled emission which has been introduced as a novel biosensing technology for detecting biosensors and biochips.
  44. Breast Cancer Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 25% to 30% BC patients and has important function in cancer progression. Recent studies have validated the value of HER2 detection for BC treatment and prognosis. Compared with the golden standard method of fluorescence in situ hybridization (FISH), the advantages of QD-based IHC have been well documented. This method is easier, cheaper and less time-consuming. Various studies have reported the successful detection for BC by QD-HER2 conjugates. This approach has been extended to selectively label MCF-7 and BT-474 BC cells for HER2, epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), and mammalian target of rapamycin (m-TOR) by visible and NIR QDs which indicated that QD-based nanotechnology is an efficient approach to offer multiplexed cancer biomarker imaging in situ on intact tumor tissue specimens for tumor pathology study at the histological and molecular levels simultaneously. BC was successfully detected with QD-based probes which demonstrated that lower expression of HER2 could be clearly detected by QD-IHC compared with conventional IHC. Thus, QD-based multiplexed imaging will provide more information for the individual events of tumor, personalized diagnosis, prognosis, and treatment
  45. Ovarian cancer QDs can also be used to detect the ovarian carcinoma marker CA125 in different types of specimens, such as fixed cells, tissue sections, and xenograft piece. Additionally, the photostability of QD signals is more specific and brighter than that of conventional organic dye. Liu et al. synthesized pH-sensitive photoluminescent CdSe/ZnSe/ZnS QDs in SKOV-3 human ovarian cancer cells that are pH-dependent, suggesting applications for intracellular pH sensors.
  46. Gastrointestinal cancer Bostick et al. detected five biomarkers on the same tissue slide by QD-based multiplexed imaging. both efficient and convenient, takes only 7 h to analyze five biomarkers, which was advantageous for clinical application. Pancreatic cancer QD-based imaging probes can target pancreatic cancer at a very early stage with the help of proteins/peptides directed against over-expressed surface receptors on cancer cells/tissues, such as transferring receptor, antigen claudin-4, and urokinase plasminogen activator receptor. Both CdSe/CdS/ZnS QDs and non-cadmium-based QDs with improved photoluminescence efficiency and stability as optical agents have been used for the imaging of pancreatic cancer cells using transferring and anti-Claudin-4.
  47. In vivo Tumor imaging Directly demonstrate the evolution mechanism of tumor progression. More convincing evidence could be obtained from in vivo tumor imaging compared with in vitro molecular imaging. Sensitive and specific imaging agents are required for high-quality in vivo tumor imaging and less biological impacts on the animal model. QD-based imaging agents can meet this demand by “enhanced permeability and retention” (EPR) or targeted molecular imaging. The principle of EPR-based tumor imaging is the leakiness of tumor blood vessels. Compared with normal tissues, tumor vasculature is quantitatively higher, but irregular, leaky, dilated, and vascular endothelial cells are poorly aligned. The morphology results in increased leakage of macromolecules and nanocarriers out of the circulatory system into the tumor tissue. These finally accumulate in the tumor microenvironment because of the lack of lymphatic drainage. Many studies have reported that non-targeted QDs can be used for cell trafficking, vasculature imaging, sentinel lymph node (SLN) mapping, and neural imaging.
  48. SLN diagnosis contributes to operation strategy in cancer surgery. During lymph node metastasis, cancer cells first reach the SLN via lymph flow. The cancer cells can be detected with high sensitivity in the SLN connected to the tumor site. The superiority of NIR QDs has been demonstrated in SLN mapping, a common procedure in BC surgery, whereby the lymph node closest to the targeted organ is monitored for the presence of locally disseminated cancer cells. Recently highly sensitive, real-time intra-operative SLN mapping of the gastrointestinal tract by NIR QDs allowing image guidance throughout the entire procedure, virtually free of any background have been reported. These findings contribute to our understanding of metastasis, which remains a fundamental barrier to the development of effective cancer therapy. Given the high sensitivity and penetration of NIR QD fluorescence, the application of QD-based SLN mapping allows the surgeon to define the tumor border accurately and minimize the size of the dissection. QDs need to be effectively, specifically, and reliably directed to a specific organ or disease site without alteration to make them more beneficial for biomedical applications. Specific targeting can be achieved by attaching targeting molecules to the QD surface.
  49. Standard protocols for in vivo imaging of liver cancer xenograft animal models have been developed. Animal imaging by injecting human hepatocellular carcinoma cell lines (HCCLM6) that overexpress alpha-fetoprotein (AFP) with antiAFP monoclonal antibody and QD-IgG probes has been established. HCCLM6 has increased potential for lung metastasis, thus it allows construction of a platform for the early monitoring of cancer metastasis