🔬Nanobiotechnology Unit 1 – Nanomaterials and Fabrication Techniques

Fundamentals of Nanomaterials

• Nanomaterials have at least one dimension in the nanoscale range (1-100 nm)
• Exhibit unique properties compared to bulk materials due to high surface area to volume ratio
• Quantum effects become significant at the nanoscale influencing optical, electrical, and magnetic properties
• Can be classified based on their dimensionality: 0D (quantum dots), 1D (nanotubes, nanowires), 2D (graphene, nanosheets), and 3D (nanoparticles, nanocomposites)
• Possess a large fraction of surface atoms leading to increased reactivity and catalytic activity
• Display size-dependent properties such as melting point depression and enhanced mechanical strength
• Nanomaterials can be synthesized through top-down (lithography, etching) or bottom-up (self-assembly, chemical synthesis) approaches

Types of Nanomaterials in Biotech

• Carbon-based nanomaterials include fullerenes, carbon nanotubes (single-walled and multi-walled), and graphene
  • Fullerenes have a hollow cage-like structure and can be functionalized for drug delivery
  • Carbon nanotubes possess high aspect ratio, mechanical strength, and electrical conductivity making them suitable for biosensors and tissue engineering scaffolds
• Metallic nanoparticles such as gold, silver, and iron oxide have unique optical and magnetic properties
  • Gold nanoparticles exhibit surface plasmon resonance and can be used for targeted drug delivery, photothermal therapy, and bioimaging
  • Silver nanoparticles have antimicrobial properties and are used in wound dressings and medical devices
• Semiconductor nanocrystals (quantum dots) have size-tunable optical properties and are used in bioimaging and biosensing
• Polymeric nanoparticles (liposomes, dendrimers) are biodegradable and biocompatible making them ideal for drug delivery and gene therapy
• Silica nanoparticles have a porous structure and can be functionalized with biomolecules for targeted delivery and biosensing

Key Properties at the Nanoscale

• Nanomaterials have a high surface area to volume ratio leading to increased reactivity and catalytic activity
• Quantum confinement effects become significant at the nanoscale resulting in discrete energy levels and size-dependent optical properties
• Surface plasmon resonance in metallic nanoparticles enables enhanced optical absorption and scattering
• Nanomaterials exhibit enhanced mechanical properties such as high strength and flexibility compared to bulk materials
• Magnetic nanoparticles display superparamagnetism enabling their use in targeted drug delivery and hyperthermia therapy
• Nanomaterials have tunable surface chemistry allowing for functionalization with biomolecules (antibodies, peptides) for targeted delivery and sensing
• Nanoscale size enables cellular uptake and interaction with biological systems at the molecular level

Nanofabrication Techniques

• Top-down approaches involve sculpting nanomaterials from bulk materials using lithography and etching techniques
  • Photolithography uses light to pattern nanoscale features on a substrate
  • Electron beam lithography offers higher resolution but is slower and more expensive
  • Focused ion beam milling can directly fabricate nanostructures by removing material
• Bottom-up approaches involve building nanomaterials from atomic or molecular precursors through self-assembly and chemical synthesis
  • Chemical vapor deposition (CVD) involves the deposition of gaseous precursors onto a substrate to form nanomaterials such as carbon nanotubes and graphene
  • Sol-gel processing involves the formation of a colloidal suspension (sol) that undergoes gelation to form a network of nanoparticles
  • Templated synthesis uses porous materials (zeolites, anodic alumina) as templates to guide the growth of nanomaterials
• Nanoimprint lithography is a high-throughput technique that involves pressing a mold with nanoscale features onto a resist-coated substrate
• Dip-pen nanolithography uses an atomic force microscope (AFM) tip to directly write nanoscale patterns by depositing molecules onto a substrate

Characterization Methods

• Electron microscopy techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM) provide high-resolution imaging of nanomaterials
  • SEM uses a focused electron beam to scan the sample surface and generate topographical and compositional information
  • TEM uses a high-energy electron beam to transmit through a thin sample and provide internal structural information
• Atomic force microscopy (AFM) uses a sharp tip to scan the sample surface and measure topography, adhesion, and mechanical properties at the nanoscale
• X-ray diffraction (XRD) provides information on the crystal structure, phase composition, and size of nanomaterials
• Dynamic light scattering (DLS) measures the hydrodynamic size and size distribution of nanoparticles in suspension
• Zeta potential measurements provide information on the surface charge and stability of nanoparticles in solution
• UV-visible spectroscopy is used to characterize the optical properties (absorption, scattering) of nanomaterials
• Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy provide information on the chemical composition and functional groups present in nanomaterials

Biomedical Applications

• Targeted drug delivery systems use functionalized nanoparticles to selectively deliver drugs to diseased cells while minimizing side effects
  • Nanoparticles can be designed to respond to specific stimuli (pH, temperature, magnetic field) for controlled drug release
  • Multifunctional nanoparticles can combine diagnostic and therapeutic capabilities (theranostics) for personalized medicine
• Nanomaterials are used in tissue engineering scaffolds to mimic the extracellular matrix and promote cell adhesion, proliferation, and differentiation
• Nanoparticle-based contrast agents enhance the sensitivity and specificity of bioimaging techniques such as MRI, CT, and optical imaging
• Nanobiosensors use nanomaterials (carbon nanotubes, graphene, gold nanoparticles) as transducers to detect biomolecules (proteins, DNA) with high sensitivity and selectivity
• Antimicrobial nanomaterials (silver nanoparticles, chitosan nanoparticles) are used in wound dressings, medical devices, and water purification to prevent bacterial infections
• Nanoparticle-based vaccines deliver antigens and adjuvants to immune cells for enhanced immune response and protection against infectious diseases

Safety and Ethical Considerations

• Nanomaterials may have potential toxicity and adverse health effects due to their small size and unique properties
  • Nanoparticles can cross biological barriers (blood-brain barrier, placenta) and accumulate in organs leading to toxicity
  • Inhalation of nanomaterials can cause respiratory issues and inflammation
• Nanomaterials may have environmental impacts such as bioaccumulation in the food chain and persistence in the ecosystem
• Occupational exposure to nanomaterials during synthesis and handling may pose health risks to workers
• Ethical considerations include the equitable access to nanomedicine, privacy concerns related to nanobiosensors, and the potential misuse of nanotechnology (nanoweapons)
• Regulatory frameworks and safety guidelines are needed to ensure the responsible development and use of nanomaterials in biotech
• Life cycle assessment and risk-benefit analysis should be conducted to evaluate the long-term implications of nanomaterials

Future Trends and Challenges

• Development of smart nanomaterials that can respond to multiple stimuli and perform complex functions (drug delivery, sensing, actuation)
• Integration of nanomaterials with other technologies such as 3D printing, robotics, and artificial intelligence for advanced biomedical applications
• Exploration of novel nanomaterials such as 2D materials (MXenes, transition metal dichalcogenides) and metal-organic frameworks (MOFs) for biomedical applications
• Scaling up the production of nanomaterials while maintaining quality, reproducibility, and cost-effectiveness
• Addressing the safety and regulatory challenges associated with the clinical translation of nanomedicine
• Developing standardized characterization methods and quality control measures for nanomaterials used in biomedical applications
• Investigating the long-term fate and biodegradation of nanomaterials in the body and the environment
• Fostering interdisciplinary collaboration between material scientists, bioengineers, clinicians, and regulatory agencies to accelerate the development and translation of nanobiotechnology