Grady Lab

Research

Biofilms on Implants

The characterization of biofilm adhesion is prohibited by the collective nature of pathogenic germs that can act as individuals on a small scale scale or a solid film on a macroscale. These multiscale phenomena make a biofilm very difficult to load as the germ-germ cohesion typically fails before the biofilm-implant adhesive strength can be measure. We use multi-scale experimental mechanics techniques to load biofilm-substrate interfaces to determine ideal surface characteristics that decrease biofilm adhesion. Improving our understanding of mechanisms used by microorganisms to adhere to various surfaces will provide a basis for better strategies for biofilm treatment and prevention.


Biofilms in Microgravity

Biofilm growth has been observed in Soviet/Russian (Salyuts and Mir), American (Skylab), and International (ISS) Space Stations, sometimes jeopardizing key equipment like spacesuits, water recycling units, air filters, radiators, and navigation windows. Several pathogens pose a risk to the health of astronauts during space missions. For example, Staphylococcus aureus is an opportunistic pathogen prevalent on human skin, is prominent in healthcare-associated infections, and was found aboard several space missions. Like most infections, staph infections are treated with antibiotics. However, space-grown biofilms exhibit increased antibiotic resistance. Therefore, there is a need to understand S. aureus biofilm characteristics and their relationship to antibiotic resistance to help enable safe, long duration, human space missions.


Cell Wall Mechanics

Enterococcus faecalis is one of the most common nosocomial pathogens in healthcare setting worldwide. This Gram-positive bacterium causes a variety of infections including urinary tract infections, endocarditis, bacteremia, cellulitis and wound infections. Therefore, there is a critical need to develop novel therapeutics to control infections associated with enterococcus faecalis. One promising target is biosynthesis pathways that contribute to the cell wall. The cell wall of Enterococcus faecalis consists of multiple peptidoglycan (PepG) layers decorated with two carbohydrate-based polymers, wall teichoic acid and a rhamnopolysaccharide. The goal of the proposed study is to understand the contribution of wall teichoic acid toward antimicrobial resistance and cell wall morphology of Enterococcus faecalis.


Microelectronic Interfaces

An internal LED board that spent approximately nine years aboard the International Space Station (ISS) is being studied in conjunction with industry partner Faradine Systems, to determine whether industry-grade hardware is adversely affected by space’s radiation levels. The project, “Light-module Interface Testing and Evaluation University Partnership”—or, LITE-UP, is funded by a NASA Established Program to Stimulate Competitive Research (EPSCoR) grant and serves as a pilot for a recently launched NASA EPSCoR Rapid Response Research (R3) program.


Intracellular Nanoparticle Dynamics

Grady et al. Soft Matter 2017

The cell interior is a very crowded chemical space, which limits the diffusion of molecules and organelles within the cytoplasm and therefore affects the rates of chemical reactions. We provide insight into the relationship between non-specific intracellular diffusion and cytoskeletal integrity. Quantum dots enter the cell through microinjection and their spatial coordinates are captured by tracking their fluorescence signature as they diffuse within the cell cytoplasm. We use single particle tracking to investigate intracellular diffusion of non-specific nanoparticle payloads with implications for drug delivery and trafficking.


Understanding Cell Health Through Mechanical Evaluation

Grady et al. Proceedings of the Society of Experimental Mechanics 2017
Grady et al. Mechanical Behavior of Biomedical Materials 2016

The interdependence of cell elasticity and cytoskeletal components is a critical step toward understanding the mechanics of living tissue.  Cellular responses and their microarchitecture react and adapt to their environment and disease state.  Changes in cell elasticity have been implicated in the pathogenesis of many human diseases including vascular disorders, malaria, sickle cell anemia, arthritis, asthma, and cancer. Therefore, there is a practical need to measure cell mechanics quantitatively to understand how diseased cells differ from healthy ones.  In particular, investigating the mechanical properties of cancer cells may help to better understand the physical mechanisms responsible for cancer metastasis. We use Atomic Force Microscopy to evaluate the mechanical properties of healthy, stressed, and deranged cells to correlate biophysical responses with changes in mechanical properties. This work includes using AFM techniques, nano-injection, and QCM-D (quartz crystal microbalance with dissipation).


Cell Nano-Injection

Cell injection is one of the core methods to introduce non-permeable molecules into cells.  It allows direct access to the two main intracellular compartments, the nucleus and cytoplasm. The video above shows dye (for visualization) being injected into living human dermal fibroblast cells. Cell injection is used in conjuction with AFM and other biophysical imaging techniques to connect the cell elasticity to overall cell health.


Tailoring of Interfaces Using Self-assembled Monolayers

Grady et al. Langmuir 2014
Losego et al. Nature Materials 2012

Self-assembled monolayers have generated strong interest in tribological systems, but are specifically of interest in the role they play in micro and nano-electronics.  In such device systems, SAMs are used to bridge from substrate to thin film and the ability to control the molecular bonding of the SAMs to thin film layer has an impact on the overall adhesion.  The selectivity of the self-assembled monolayer chemistries can be useful in controlling interfacial thermal conductance as well.


Mechanophore-functionalized Interfaces

Grady et al. ACS Applied Materials & Interfaces 2014

A new class of stimuli-responsive polymers have been inspired from biomimetic systems by channeling mechanical energy to initiate a chemical response.  This class of material incorporates a molecule termed a mechanophore into a polymer where mechanical energy is used to activate chemical pathways within the polymer.  The strategy for this work is to incorporate a mechanophore known as spiropyran, which provides evidence of a local chemical reaction at critical interfaces within thin film coatings.


Autonomic Restoration of Conductivity

Blaiszik et al. Advanced Materials 2012

The demand for smaller electronics with increased performance and functionality drives the development of complex, high-density integrated circuits and robust packaging that operate in adverse environments. We use microencapsulated liquid metals dispersed in a dielectric material to demonstrate autonomic healing of an electrical circuit with extremely quick recovery of conductance after the damage event. The restorative mechanism relies on the triggered release and transport of a compartmentalized liquid metal into the broken conductive pathway. Crack damage in the multilayer specimen ruptures the capsules, liquid metal flows into the broken circuit, and conductivity is restored. This autonomic healing concept has the potential to create more sustainable electronic devices through increased fault-tolerance, improved circuit reliability, and extended service life in challenging mechanical environments.


Interfacial Adhesion of a Photodefinable Polyimide

Grady et al. Thin Solid Films 2014

Polyimide films are commonly used as passivation layers, interlayer dielectrics, and protective layers in integrated circuits. The added photodefinable capability of spun-cast polyimide films reduces the number of processing steps and serves as a promising option for microelectronics.  Thermal mismatch at the polyimide/substrate interface can produce significant stresses causing the layers to debond, reducing the overall reliability of microelectronic components.  Processing steps unique to photodefinable polyimides and substrate passivation layer also affect fracture resistance of the interface.  Understanding and predicting the adhesion at critical interfaces is necessary for the design of a robust and well-adhered film.  The interfacial strength of blanket polyimide films are measured using the laser spallation technique.

Additionally, the interfacial fracture energy of polyimide on silicon is assessed using a dynamic delamination protocol.  The photodefinability of the polyimide is utilized to pattern films into strips over a weak-adhesion layer.  Laser induced stress waves are used to channel kinetic energy into debonding the polyimide-substrate interface.  This high toughness would be difficult to quantify by more conventional test methods.