From microscopy to x-rays to ultrasound to magnetic resonance imaging (MRI), engineering plays a key role in advancing fundamental biological research and medical treatment. MRI has rapidly become of the most widely used medical imaging and diagnostic tools.  Not requiring any ionizing radiation, it can benignly probe deep within the body, offering excellent soft tissue contrast and high-resolution imaging. Together with related NMR technologies it also remains one of the most successful examples of the translation of fundamental physics and engineering into useful application across multiple food, pharmaceutical, chemical, energy, and of course, biomedical industries.

But there remains much room for engineering to still advance the capabilities of such technologies. As examples, this talk will focus on how micro and nanofabrication technologies, traditionally associated with semiconductor industries, can be exploited to enhance NMR / MRI functionality,  boosting in vivo imaging power and adapting the technologies for novel biosensing applications. Specifically, this talk will consider how microfabricated magnetic and smart-polymer micro and nanostructures can (i) increase NMR imaging contrast 10 to 100-fold for deep in vivo quantitative tracking of individual biological cells, (ii) enable “color” MRI to augment traditional monochrome “grayscale” imaging, and (iii) allow new radio-frequency addressable nanosensors for remotely detected in vivo or embedded sensing applications.

Presentation will be at an introductory level; no prior knowledge of NMR / MRI required.

Cavitation events, or the formation of a gas pocket in a liquid medium, can be highly destructive and disruptive. We have sought to understand how surfaces can facilitate or inhibit cavitation by examining the structure-property relationships that give rise to efficient bubble nucleation. These approaches in turn underlie our new technologies in imaging, therapy, and protective coatings.

First, the formation of bubbles in solution can be used as efficient ultrasound contrast agents. Because of their high compressibility and low density, bubbles offer excellent contrast in aqueous media. However, microbubbles suffer from low stability and an inability to leave the bloodstream. In this work, we engineered functionalized silica nanoparticles that could facilitate the formation of transient microbubbles in response to an incoming acoustic wave.

Second, acoustic cavitation on nanoparticle surfaces gives rise to many therapeutic applications. Non-equilibrium bubble collapse is a violent process that concentrates both thermal and mechanical energy capable of not only killing cells but transporting nanoparticles through dense media such as extracellular matrix. Notably, the propulsion of nanoparticles can kill cells up to hundreds of microns away, thereby addressing transport limitations in solid tumors.

Third, we sought to rationally design surfaces that could retard cavitation as well. Solutions of protein therapeutics are known to form particulates upon impact and resulting cavitation. These particulates can in turn induce an anaphylactic response in patients, in some cases leading to patient death. Here, new coatings were applied to standard glass vials to reduce their tendency towards cavitation, thereby protecting the proteins in solution from irreversible aggregation.

Abstract:
The extracellular matrix (ECM) provides structural scaffolding and mediates signaling in the extracellular space. The protein component is resistant to chaotrope extraction, making proteomic characterization challenging. We have developed optimized protocols for extraction of ECM that have been refined using samples from many systems, allowing for molecular-scale assessment of ECM proteome composition and architecture. We currently use these methods with the help of collaborators to assess ECM remodeling in wound healing, anti-aging models, tumor progression and regenerative medicine applications. The focus of this presentation will be the methods used and common features found in wound healing and disease processes.

Abstract:
Microbial natural products continue to have a profound impact on human health. While environmental natural products are widely used in medicine, structurally related metabolites are an integral component of the ‘language’ microbes use to interact within human microbiome communities. These chemical signals act as directives to neighboring microbes, which influence how the microbiome responds to environmental changes. We aim to understand the ecological roles of natural products in the development and persistence of chronic infections, specifically between members of the cystic fibrosis pulmonary microbiota and elucidate their functional roles in community dynamics. To do this, we develop and apply analytical methods to analyze microbial metabolomics methods and develop culturomics tools to enable long-term growth of the microbiome to mimic the chronic lung infections observed in cystic fibrosis.

Abstract:

Pulmonary arterial hypertension (PAH) is a form of a pulmonary vascular disease that causes high blood pressure in the lungs. It results in scarring of the small blood vessels, leading to impaired blood flow and increased blood pressure. Over time, this increase in blood pressure causes damage to the heart. This disease is four times more likely to impact women than men and women but the mechanisms underlying these sex differences remain unknown. Studies to improve our understanding of the mechanisms underlying sex differences in PAH could be accelerated by cell-culture tools that reproduce key aspects of human physiology, i.e., the complex 3D geometry of pulmonary vasculature and time-dependent changes in extracellular matrix mechanical properties that occur during disease progression. To overcome these limitations, we designed a novel biomaterial that is initially soft like healthy blood vessels and can be stiffened using light to mimic vessel scarring in PAH. The material is stable for long periods of time in the conditions used to grow cells and can be 3D bioprinted with cells inside to reproduce the shape of a pulmonary blood vessel. Experiments have demonstrated that stiffening in 3D results in activation of male cells but that cells derived from female patients are not as sensitive to changes in the microenvironment.