nanotech final

PVD Coatings for Orthopedic Implants

Intended to promote osseointegration, reduce wear, and minimize the release of metallic ions into the body.

Pros of Titanium Alloys in Implants

Excellent biocompatibility, corrosion resistance, low modulus of elasticity (similar to bone), good mechanical properties.

Cons of Titanium Alloys

Poor wear resistance, potential for release of metallic ions, limitations in promoting direct bone bonding.

Hydroxyapatite (HA) in Implants

Pros: Bioactive, promotes osseointegration, mimics bone mineral, encourages new bone growth.

Cons: Brittle, challenges in achieving strong adhesion to the substrate.

Diamond-like Carbon (DLC) Coatings

Pros: Excellent biocompatibility, low friction, high wear resistance.

Cons: Challenges in maintaining integrity under stress, potential delamination, complex deposition process.

Surface Topographies for Biocompatibility

Micro- and nano-scale patterns (pits, grooves) can guide cell adhesion and alignment, encouraging osteoblast alignment critical for strong bone-implant interfaces.

PVD Sputtering Technique

Can deposit a wide range of materials with high purity. Reactive sputtering enables the deposition of compounds like oxides and nitrides.

Effect of Substrate Temperature in PVD

Elevated temperatures during deposition can enhance diffusion and adhesion of the coating.

Superparamagnetism

A property where magnetic nanoparticles (e.g., iron oxide) lose their magnetization when the external magnetic field is removed.

Benefit of Superparamagnetism in Drug Delivery

Reduced aggregation (prevents clumping/blockages), improved biocompatibility (no permanent field), enhanced safety, and allows for precise control and reversible magnetization for targeted delivery.

Composition of Superparamagnetic Nanoparticles

Magnetic materials such as iron oxide (Fe3O4 or Fe2O3)

Effect of Nanoparticle Size on SPR

As nanoparticle size increases, the SPR wavelength shifts to longer wavelengths (lower resonant frequency).

Nanoparticle Size and Biosensor Sensitivity

Smaller nanoparticles have a higher sensitivity to changes in the local environment due to a larger surface area relative to volume.

Effect of Nanoparticle Shape on SPR

Different shapes (spheres, rods, triangles) have distinct SPR characteristics. Elongated shapes (nanorods) have multiple SPR modes (transverse and longitudinal) for multiplexed sensing.

Strategy to Enhance SPR Signal-to-Noise Ratio

Implementing background correction and subtraction via robust baseline stabilization and using reference channels to subtract background noise.

Techniques to Address Stability/Nonspecific Binding

Surface modification techniques like Self-Assembled Monolayers (SAMs) or Polymeric Coatings, and using Blocking Reagents to occupy unbound sites.

CNT Property: Size and Diameter

Allows CNTs to penetrate insulating protein shells and get close to enzyme active sites, facilitating direct electron transfer.

CNT Property: Electrical Conductivity

High conductivity ensures fast electron transfer rates, which is essential for maximizing the electrochemical signal and minimizing noise.

CNT Chirality and Conductivity

"Armchair" CNTs are metallic and excellent conductors. "Zigzag" CNTs can be metallic or semiconducting.

CNT Structure: Vertically Aligned Forests

Allows one end to contact the electrode and the other to interact with the electrolyte, often providing better defined electron transfer pathways and improved sensor performance.

CNT Surface Functionalization

Allows for covalent linking of biomolecules (antibodies, enzymes) through chemical groups (like carboxylic groups) for signal amplification and improved detection limits (e.g., in immunosensors).

Performance Example: CNT-mat Glucose Sensor

Demonstrated 43 times higher sensitivity than a control graphite electrode.

EPR Effect (Enhanced Permeation and Retention)

A passive targeting mechanism that relies on the physical characteristics of the tumor's vascular system for nanoparticle accumulation.

Enhanced Permeation

Tumor vessels are abnormal and "leaky" with wide fenestrations, allowing nanoparticles to extravasate (leak) into the tumor interstitium.

Enhanced Retention

Tumor tissue has impaired or non-existent lymphatic drainage, which prevents the clearance of nanoparticles once they have entered the tumor, causing prolonged retention.

Influence of Nanoparticle Size on EPR

Particles must be small enough to circulate and penetrate leaky vasculature (e.g., 80–90 nm) but large enough to avoid rapid renal filtration.

PEGylation

Coating nanoparticles with polyethylene glycol (PEG) to provide a "stealth" effect and evade the Mononuclear Phagocyte System (MPS).

Benefit of PEGylation

Significantly extends the half-life and circulation time in the bloodstream, increasing the probability of accumulation via the EPR effect.

Active Targeting Example

Modifying nanoparticles with ligands that target Transferrin Receptors or Folate Receptors, which are often over-expressed in cancer cells.

Role of Zeta Potential in Stability

Nanoparticles with a high zeta potential generally exhibit greater electrostatic repulsion, resulting in enhanced colloidal stability by preventing aggregation or coagulation.

Zeta Potential and Cellular Uptake

The zeta potential influences interactions with cell membranes. Moderately high positive or negative values may promote strong interactions and efficient cellular internalization.

Function of DLS in Nanomedicine

It is a valuable tool for understanding the relationship between surface charge (zeta potential) and hydrodynamic diameter, enabling the precise manipulation of these parameters for enhanced stability, biocompatibility, and targeted functionality.

Secondary Electrons (SE) Signal

Sensitive to surface morphology, topography, and electrical conductivity. Provides high-resolution images that highlight fine surface details, textures, and structural variations.

Backscattered Electrons (BSE) Signal

Provides insights into the sample's elemental composition, atomic density, and crystal structure. Intensity is influenced by the atomic number of the elements present.

Integration of SE and BSE Signals

Allows researchers to correlate surface morphology with elemental composition for comprehensive material characterization (e.g., surface roughness, composition gradients).

AFM Driving Principle

Works by detecting atomic-scale forces (e.g., Van der Waals) between a sharp probe tip and the sample surface, using the deflection of a cantilever to measure these forces.

Contact Mode in AFM

Tip is pressed against the surface; uses strong, short-range repulsive forces. Suitable for rigid or fixed samples (e.g., hard biomaterials) due to risk of sample damage/shear forces.

Non-Contact (Tapping) Mode in AFM

Cantilever oscillates, tip briefly taps the surface; minimizes lateral forces. Ideal for soft and delicate samples (e.g., live cells, lipid membranes, hydrogels).

Ideal Cantilever Properties

Light, flexible, high resonance frequency, and a sharp, stable tip with a small radius of curvature to ensure sensitive and accurate, high-resolution measurements.

AFM Resolution Dependence

Primarily dependent on tip sharpness (radius of curvature of the tip's apex), accurate measurement/control of interaction forces, and the stability of the system.

AFM Force Spectroscopy Mode

Pressing the tip into and retracting from a single molecule to measure nanomechanical properties (stiffness, elasticity) and the forces required to unfold proteins or quantify binding strength (molecular recognition).

XRD Application: Crystal Structure Determination

Used to identify the crystal structure and lattice parameters of nanomaterials by comparing diffraction patterns with reference data.

XRD Application: Grain Size Analysis

Uses the Scherrer equation to analyze the broadening of diffraction peaks, allowing for the estimation of the average crystallite size of nanomaterials.

XRD Application: Phase Analysis

Enables the identification of different crystalline phases present in a nanomaterial sample, allowing researchers to determine the composition and phase purity.

Photolithography Challenge: Diffraction Limit

The wavelength ($\lambda$) of the light source (EUV: $\lambda \approx 13.5$ nm) is a fundamental constraint; diffraction causes light to spread and blur the pattern as feature size approaches $\lambda$.

Alternative: Electron Beam Lithography (EBL)

Completely overcomes the diffraction limit by using a focused beam of electrons (shorter de Broglie wavelength), allowing for features below 10 nm.

Alternative: Nanoimprint Lithography (NIL)

A non-optical, mechanical replication method that presses a master stamp into a polymer. Resolution is determined by the stamp's features, independent of light wavelength.

Alternative: Two-Photon Polymerization

Uses infrared femtosecond lasers and non-linear optics so polymerization only occurs at the focus point; enables the creation of intricate 3D structures and avoids the lateral spread of single-photon absorption.

Function of Argus II System

Bypasses defunct light-sensing photoreceptor cells and directly stimulates the remaining viable retinal neurons to generate visual perception (phosphenes).

Camera Role (on glasses)

Acts as a substitute for damaged photoreceptors by capturing the visual scene.

Video Processing Unit (VPU) Role

Processes the raw image data into a series of small, optimized electrical pulses (a low-resolution "brightness map"), which is transmitted wirelessly.

Retinal Electrode Array Role

A sheet of 60 electrodes surgically tacked to the retina (epiretinal placement) that delivers electrical pulses to surviving inner retinal cells (ganglion/bipolar cells), causing them to generate action potentials.

Limitation: Resolution Limit

Argus II uses only 60 electrodes compared to $\approx 1$ million ganglion cells, resulting in low-definition vision where patients perceive boundaries/outlines but not sharp visual acuity.

Limitation: Retinal Health

Only works for patients whose optic nerve and inner retinal architecture are intact.

Glaucoma

Progressive damage to the optic nerve, initially destroying peripheral vision and potentially leading to blindness; treatment focuses on high or unstable intraocular pressure (IOP).

Importance of Continuous IOP Monitoring

Crucial because optic nerve damage is permanent; catching elevated IOP peaks and monitoring the natural 24-hour IOP curve allows for optimized, personalized treatment plans.

Emerging Tech: Smart Contact Lenses

Soft, disposable lenses with an embedded MEMS sensor and microprocessor (ASIC) that use circular active and passive strain gauges to measure corneal curvature changes (related to IOP).

mRNA Vaccine Mechanism

The mRNA provides instructions to the body's cells (e.g., muscle cells) to make a specific viral protein (e.g., the Spike protein), which is then displayed to the immune system.

Immune Response Triggered by Vaccine

The display of the Spike protein causes the body to create antibodies that will fight the actual virus if a later infection occurs.

Role of Liposomes (Lipid Nanoparticles)

Acts as a carrier/delivery system, often formed as Cationic Liposomes (positively charged) to bond electrostatically with the negatively charged mRNA.

Function of Liposomes in Delivery

Forms stable lipoplexes to protect the fragile mRNA and facilitate its uptake into the body's cells through endocytosis.

Role of Cholesterol in Liposomes

Incorporated to increase the liposome's membrane packing density and stability, thereby improving overall vaccine efficacy.

Designed Peptide Sequence

$\text{Dex-FF – DXR/Taxol – S–S – EE – RGD}$

Dex-FF

Combination of the Anti-Inflammatory Drug (Dexamethasone) and the Assembly Motif for local therapeutic effect at the tumor site.

FF (Diphenylalanine)

The core Self-Assembly Motif that spontaneously forms the nanofiber hydrogel scaffold for drug encapsulation.

DXR/Taxol

The Anti-Cancer Drug Payload that is released intracellularly upon the cleavage of the disulfide bond.

S–S (Disulfide Bond)

The Controlled Release Linker that is cleaved in the reducing environment (high glutathione) of the tumor cell cytosol, releasing the DXR/Taxol payload.

EE (Glutamic Acid Pair)

Amino acids used for Structural Stability and potential $\text{pH}$-responsiveness within the self-assembled hydrogel structure.

RGD (Arginine-Glycine-Aspartic acid)

The Targeting Ligand that binds to integrin receptors overexpressed on the surface of tumor cells for active targeting

EPR Effect (in relation to this design)

The passive mechanism by which the entire nanostructure first accumulates in the tumor via leaky vasculature and poor lymphatic drainage.