Nanomaterial Fabrication, Imaging, and Drug Delivery Applications
Chemical Vapor Deposition (CVD) Fundamentals
Chemical vapor deposition (CVD), a hybrid method using chemicals in the vapor phase, is conventionally used to obtain coatings of a variety of inorganic or organic materials. It is widely used in industry because of relatively simple instrumentation, ease of processing, the possibility of depositing different types of materials, and economical viability. Under certain deposition conditions, nanocrystalline films or single crystalline films are possible.
CVD Process and Variants
There are many variants of CVD, including:
- Metallo-Organic CVD (MOCVD)
- Atomic Layer Epitaxy (ALE)
- Vapor Phase Epitaxy (VPE)
- Plasma Enhanced CVD (PECVD)
These variants differ in source gas pressure, geometrical layout, and temperature used. The basic CVD process, however, can be considered as a transport of reactant vapor or reactant gas towards the substrate, which is kept at some high temperature. Here, the reactant cracks into different products that diffuse on the surface, undergo a chemical reaction at an appropriate site, nucleate, and grow to form the desired material film. The by-products created on the substrate must be transported back to the gaseous phase, removing them from the substrate. Vapors of the desired material may often be pumped into the reaction chamber using a carrier gas. In some cases, reactions may occur through aerosol formation in the gas phase.
CVD can proceed through various processes such as reduction of gas, chemical reaction between different source gases, oxidation, or some disproportionate reaction. However, it is preferable that the reaction occurs at the substrate rather than in the gas phase. Usually, temperatures of 300–1,200 °C are used at the substrate.
Substrate Heating Methods in CVD
There are two primary ways substrates are heated: ‘hot wall’ and ‘cold wall’ setups.
Hot Wall vs. Cold Wall CVD Setups
In a hot wall setup, deposition can take place even on reactor walls. This is avoided in cold wall designs. Additionally, reactions can occur in the gas phase with a hot wall design, which is suppressed in a cold wall setup. Furthermore, coupling of plasma with chemical reactions in a cold wall setup is feasible. Usually, gas pressures in the range of 100–105 Pa are used.
Factors Affecting CVD Growth Rate and Film Quality
Growth rate and film quality depend upon the gas pressure and the substrate temperature. When growth takes place at low temperatures, it is limited by the kinetics of surface reaction. At intermediate temperatures, it is limited by mass transport, i.e., the supply of reacting gases to the substrate, where the reaction is faster and the supply of reactants is slower. At high temperatures, the growth rate reduces due to desorption of precursors from the substrate. When two types of atoms or molecules, say P and Q, are involved in the desired film, there are two ways in which growth can take place.
High Energy Ball Milling for Nanoparticle Synthesis
High energy ball milling is one of the simplest ways of making nanoparticles of some metals and alloys in powder form.
Ball Milling Process and Parameters
There are many types of mills, such as planetary, vibratory, rod, and tumbler. Usually, one or more containers are used at a time to make large quantities of fine particles. The size of the container, of course, depends upon the quantity of interest. Hardened steel or tungsten carbide balls are put into containers along with powder or flakes (<50 µm) of the material of interest. The initial material can be of arbitrary size and shape. The container is closed with tight lids. Usually, a 2:1 mass ratio of balls to material is advisable. If the container is more than half-filled, the efficiency of milling is reduced. Heavy milling balls increase the impact energy on collision. Larger balls used for milling produce smaller grain size but larger defects in the particles.
Controlling Particle Size and Purity
The process, however, may add some impurities from the balls. The container may be filled with air or inert gas. However, this can be an additional source of impurity if proper precaution to use high purity gases is not taken. A temperature rise in the range of 100–1,100 °C can occur. Gases like O2, N2, etc., can be sources of impurities as constantly new, active surfaces are generated. Cryocooling is sometimes used to dissipate the heat generated. During milling, liquids can also be used.
Types of Ball Mills and Operational Aspects
The containers are rotated at high speed (a few hundreds of RPM) around their own axis. Additionally, they may rotate around some central axis and are therefore called ‘planetary ball mills’. When the containers are rotating around the central axis as well as their own axis, the material is forced to the walls and is pressed against the walls. By controlling the speed of rotation of the central axis and container, as well as the duration of milling, it is possible to grind the material to fine powder (few nm to few tens of nm) whose size can be quite uniform.
Nanoparticle Nucleation and Colloidal Synthesis
The process of nucleation is a ‘bottom-up’ approach in which atoms and/or molecules come together to form a solid.
Understanding Nucleation Processes
The process can be spontaneous, and it may be homogeneous or heterogeneous nucleation.
Homogeneous and Heterogeneous Nucleation
Homogeneous nucleation is said to take place when it involves nucleation around the constituent atoms or molecules of the resultant particles. Heterogeneous nucleation, on the other hand, can take place on a foreign particle like dust, deliberately added seed particles, templates, or the walls of the container.
Cavitation-Induced Nucleation
Nucleation can also occur by a cavitation process. In cavitation, if there are some bubbles in the solution which then collapse, the high local temperature and pressure thus generated may be sufficient to cause homogeneous nucleation. The nucleation process is controlled.
Colloidal Synthesis of Semiconductor Nanoparticles
Compound semiconductor nanoparticles can be synthesized by a wet chemical route using appropriate salts. Sulfide semiconductors like CdS and ZnS can be synthesized as nanoparticles simply by coprecipitation.
Surface Passivation and Chemical Capping
These nanoparticles need to be surface passivated as colloids formed in liquids have a tendency to coagulate or ripen due to attractive forces existing between them. The electrostatic and other repulsive forces may not be sufficient to keep them apart. Steric hindrance can be created by appropriately coating the particles to keep them apart. This is often known as ‘chemical capping’.
Advantages of Colloidal Synthesis
An advantage of this chemical route is that one can get stable particles of a variety of materials not only in solution but even after drying off the liquid. One can even make thin films of the capped particles by spin coating or dip coating techniques. The coating, however, has to be stable and non-interactive with the particle itself, except at the surface. Coatings may be a part of post-treatment or a part of the synthesis reaction to obtain nanoparticles. If it is a part of the synthesis reaction, the concentration of capping molecules can be used in two ways: to control the size as well as to protect the particles from coagulation.
Electron Microscopy: Backscattered Electrons (BSE)
BSE Definition and Role in FESEM
Definition: Backscattered electrons are high-energy electrons from the primary electron beam that are elastically scattered back out of the sample after interacting with the sample’s atomic nuclei.
Role in FESEM:
- Compositional Contrast:
- BSE intensity depends on the atomic number (Z) of the sample’s elements. Higher-Z elements (e.g., metals like Au, Ag) scatter more electrons, appearing brighter in BSE images, while lower-Z elements (e.g., carbon, polymers) appear darker.
- This enables material contrast, distinguishing phases or regions with different compositions (e.g., identifying metal nanoparticles embedded in a polymer matrix).
- Subsurface Information:
- BSE originate from deeper within the sample (up to ~1 μm, depending on beam energy and material), providing information about subsurface features and composition, unlike SE, which are surface-sensitive.
- Quantitative Analysis:
- BSE images are used for quantitative compositional analysis when combined with techniques like Energy-Dispersive X-ray Spectroscopy (EDS). For example, mapping the distribution of heavy elements in a composite material.
- Applications:
- Analyzing alloys, geological samples, or multilayered materials where compositional differences are critical.
- Example: In a semiconductor sample, BSE can highlight doped regions (e.g., Si with P or B) due to slight atomic number variations.
Electron Microscopy: Secondary Electrons (SE)
SE Definition and Role in FESEM
Definition: Secondary electrons are low-energy electrons (<50 eV) ejected from the sample’s surface atoms due to inelastic interactions with the primary electron beam.
Role in FESEM:
- Topographical Imaging:
- SE are emitted from the top ~1–10 nm of the sample surface, making them highly sensitive to surface topography. They produce high-resolution images showing surface features like roughness, edges, and textures.
- The intensity of SE varies with the angle of the surface relative to the electron beam, enhancing edge contrast (e.g., sharp edges appear brighter).
- High-Resolution Imaging:
- Due to the high brightness and fine probe size of the field emission source in FESEM, SE imaging achieves sub-nanometer resolution, ideal for visualizing nanoparticle morphology, surface defects, or nanostructures (e.g., carbon nanotubes, graphene layers).
- Surface Sensitivity:
- SE are ideal for studying surface properties, such as coatings, thin films, or surface contamination, as they are generated from the outermost layers.
- Applications:
- Characterizing surface features of nanomaterials, biological samples, or thin films.
- Example: In ZnO nanoparticle analysis, SE imaging reveals particle shape, size, and surface texture, critical for applications like photocatalysis.
Nanoparticles in Drug Delivery Systems
Nanoparticles (NPs), typically in the size range of 1–100 nm, have revolutionized drug delivery systems due to their unique physicochemical properties, such as high surface area, tunable size, and ability to encapsulate drugs. Their applications in drug delivery enhance therapeutic efficacy, reduce side effects, and enable targeted treatment, making them highly significant in pharmaceutical applications.
Targeted Drug Delivery with Nanoparticles
NPs can deliver drugs directly to specific cells or tissues, such as cancer cells, by attaching ligands (e.g., antibodies) that bind to target receptors. This improves drug specificity and minimizes side effects.