Fellowship recipient Alfred Chang
Application for summer 2020 is closed. Material is provided for reference only.
1) Review the summer 2020 NURF project descriptions (below) and select a project of interest.
2) Complete the APPLICATION, and save the file with your last name and your first name as the first words in the file name. (Ex: Smith-Barb 2020 NURF Application)
3) By 8:00am Eastern on February 5, email your completed application and current resumé (saved with the same name convention -- Smith-Barb resumé) to the project’s faculty mentor(s) for consideration, and cc: Heidi Deethardt at email@example.com. NDnano faculty will follow-up with selected applicants directly. Award notifications will begin in early March.
Students are welcome to apply for more than one project. However, please list and prioritize on your application(s) all the projects for which you are applying. Please include project title and faculty first/last name.
For purposes of the NURF program, undergraduates are students who will not yet have completed their undergraduate studies at the start of their summer fellowship.
The University allows students to work a maximum of 40 hours per week during the summer (all campus jobs combined). This means that students cannot participate in the NURF program on a full-time basis and at the same time hold any other paid, on-campus, summer position. (Fellowships of less than 40 hours per week would be considered on a case-by-case basis.)
In addition, fellowship recipients who attend Notre Dame and have 2019-2020 on-campus, academic-year jobs may be prohibited from starting their NURF position before the last week of May; contact Heidi Deethardt for more details.
Project: Treating nitrate contamination in groundwater using nano-catalysts in the hydrogel membrane reactor
Nitrate is the most prevalent water contaminant in the world, affecting people of all socioeconomic statuses. There is a need to develop new treatment technologies that can remove nitrate from water and turn it into a nontoxic byproduct. We have developed a new technique – the catalytic hydrogel membrane reactor – and the student will assist with the further development of this technology. The student will be trained to work independently on a project that involves nano-catalyst synthesis and testing, with a specific focus on treating nitrate in tap water. As a milestone, the student will be expected to develop a poster to present at local meetings. Their work and write-ups will be included in future journal publications. The ideal student should be studying environmental engineering, chemical engineering, environmental science, or a related discipline, and should have previous experience working in a wet lab and/or nanoparticle synthesis and testing.
Project: Molecular and process design framework for the separation, recycling, and reuse of hydrofluorocarbon mixtures
Figure 1. The proposed framework integrates mixture physical property measurements, atomistic molecular simulations, process optimization, and demonstration to create innovative ionic liquid mixtures and separation processes that could enable global recycling of HFCs. The student researcher will work with a graduate student on molecular simulations and data analysis (Specific Aims 2 and 3).
Refrigerators and heat pumps use a substance called a refrigerant to transfer heat between two spaces. Prior to the late 1980s, refrigerants often contained chlorfluorocarbons, but these materials were phased out because of their high ozone depletion potential. Mixtures of hydrofluorocarbons appeared on the market as replacement. Hydrofluorocarbons (HFC) do not deplete the Earth's ozone layer, but many are potent greenhouse gases with much higher global warming potentials than CO2, prompting a concerted effort to phase out the use of high global warming potential HFCs. The phase out of these materials is complicated by the fact that there are thousands of tons of refrigerant mixtures that contain both low and high global warming potential compounds, and there is no viable method for separating and reclaiming the components. The separation of low and high global warming HFCs is complex because they are azeotropic or near-azeotropic materials, meaning they are chemically similar and behave like a single (pure) fluid. The goal of the project is to develop tools and processes that enable the separation of high and low global warming potential HFCs, allowing the recovery and reuse of the low global warming potential HFCs. To accomplish this goal, an integrated molecular and chemical process design framework will be developed to engineer novel ionic liquid-based HFC separation technologies. The approach will unify "top-down" computer-aided molecular design with "bottom-up" experimentally driven approaches to more efficiently identify new separation agents for HFC azeotropic mixtures. The engineering framework will be widely applicable to other chemical separation processes, including that of next-generation refrigerants such as hydrofluoro-olefins and hydrochlorofluoro-olefins.
The work is organized in four specific aims:
- Carry out pure and mixed gas solubility measurements of R-32, R-125 and R-134a in a wide range of ILs. (collaborator at KU)
- Conduct high throughput molecular simulations of IL solvents for HFCs. (Notre Dame)
- Systematically screen process designs and determine IL physical property targets via rigorous mathematical modeling and superstructure optimization. (Notre Dame)
- Demonstrate viability of most promising ionic liquid entrainers in lab-scale extractive distillation systems. (collaborators at KU)
As such, this research program presents an opportunity to make significant progress towards integrating molecular design and end-use application optimization. In contributing to this ambitious project, the student researcher will be asked to elucidate molecular-level phenomena governing complex IL and HFC interactions. Specifically, the student will work with a ND graduate researcher to conduct and analyze molecular simulations. Self-motivated, independent student researchers will have the ability to focus their research efforts on the aspect of the project that appeals to their skills and interests. Prior Python programming or *nix command line experience will be helpful, but comfort with any computer programming language is sufficient. Students in chemical engineering, mechanical engineering, environmental engineering, electrical engineering, and computer science are well-suited to undertake this research project.
Project: Data-driven approaches to elucidating molecular design principles for nanostructured membranes capable of separating similarly sized molecules
a. A schematic showing the physical and chemical properties of the membrane that can be tuned easily. Exploring how transport through chemically selective pores is affected when the physical and chemical interactions occur in confined geometries is critical to this project. b. Parameter estimation for a single filtration experiment. The mass of the material that permeated through the membrane was measured every 5s and is marked with red dots. Best fit parameters, directly to the nanostructural features of the membrane, were computed by minimizing difference between data and predictions.
The goal of the proposed research is to develop the fundamental scientific knowledge that informs the design and fabrication of nanostructured membranes with pore wall chemistries tailored to facilitate the separation of molecules with comparable sizes, especially rare earth elements (REEs). Membrane separations have demonstrated significant advantages in sustainability and energy efficiency. However, the majority of state-of-the-art membranes are size-selective and unable to distinguish between species of comparable molecular sizes. As such, there are significant opportunities for membranes that distinguish between molecules based on chemical, rather than steric, factors. Unfortunately, knowledge regarding the molecular design features that enable this class of transport mechanisms is lagging, which hinders the rational development of chemically selective membranes. Thus, there is a critical need to execute systematic, experimental studies on such membranes to elucidate the relationships between their nanostructure, surface chemistry, and selective transport mechanisms. Here, this engineering opportunity will be met by integrating membrane science and statistical learning paradigms into a convergent framework to develop the knowledge that guides the molecular design of these membranes. Self-assembled membranes that are amenable to post-assembly functionalization offer orthogonal control over membrane nanostructure and chemistry such that a diverse array of interfacial and transport phenomena can be interrogated. It is hypothesized that three molecular properties – solute-carrier affinity, spacer arm length, and pore diameter – control chemically selective transport mechanisms. Statistical learning and dynamic diafiltration experiments will be utilized to efficiently navigate this vast molecular design space and to elucidate the desired structure-property relationships up to 100 times faster than Edisonian searches.
The work is organized in three objectives:
- Identify molecular design strategies for copolymer membranes tailor-made to promote the efficient separation of REEs. This effort will generate a family of membranes with rationally-engineered nanostructures and pore wall chemistries.
- Develop a statistical learning framework to identify the dominant transport and interfacial phenomena from dynamic diafiltration experiments. Model-based design of experiments will be used to discern between model permutations in a proposed model hierarchy.
- Utilize statistical learning to guide the development of structure-property relationships for chemically selective transport mechanisms that are capable of separating REEs.
As such, this research program presents an opportunity to make significant progress toward elucidating the critical structure-property relationships for membranes capable of transporting target solutes based on chemical, rather than steric, factors, with applications well beyond REEs. In contributing to this ambitious, potentially transformative project, the student researcher will be asked to elucidate how the nanoscale structure and chemistry of the membranes impact the observed transport properties through experimental water flow and solute filtration tests. The student will also assist in developing new data analysis capability ultimately leading to new optimal design-of-experiments capabilities. Self-motivated, independent student researchers will have the ability to focus their research efforts on the aspect of the project that appeals to their skills and interests. Students in chemical engineering, mechanical engineering, environmental engineering, electrical engineering, and computer science are well-suited to undertake this research project.
Project: Using piezoelectric and pyroelectric crystals to directly convert motion and heat into electrical plasmas
Professor Seong-kyun Im • Aerospace & Mechanical Engineering • firstname.lastname@example.org
The technical objective of this National Science Foundation-sponsored project is to engineer devices and systems to harvest mechanical or thermal energy to directly produce an electric discharge or plasma. These plasmas can be used for applications such as water purification or pollution mitigation without the need for an electrical power supply. The key to this strategy is to utilize piezoelectric and pyroelectric crystals that can produce large voltages from vibrations or heat. The role of the student is to help design, build, and test both the mechanical and thermal harvesting systems. They will work closely with a graduate student who is focused more on the plasma generation science, and have the opportunity to do experimental work, data analysis, and potentially some computational modeling. Applicants from any science or engineering discipline are acceptable, although those with a background in electrical engineering and mechanical engineering are preferred. Students interested in continuing the research throughout the school year will be given priority.
Project: Engineering biomimetic materials to control stem cell morphogenesis
Blood and lymphatic vasculatures are two important components of the tumor microenvironments. Blood vessels supply nutrients important for tumor growth and serve as a conduit for hematogenous tumor spread, while the lymphatic vessels are used by the cancer cells to interact with the immune system as well as for lymphatic tumor metastasis. Consequently, the growth of blood and lymphatic vasculatures surrounding the tumor have been associated with tumor metastases and poor patient prognosis. The objective of this project is to understand what governs the formation of blood and lymphatic vessels from stem cells, how these processes are affected by the tumor microenvironment, and how we can use these insights to develop novel therapies. The student will synthesize and characterize biomaterials for in vitro evaluation using stem cells. The student is expected to maintain the stem cell culture, and study cell-materials interaction using microscopy and molecular biology techniques. Students with a background in mechanical engineering, chemical/bio-engineering, materials science, or biochemistry are encouraged to apply. Prior lab experience is preferred.
Project: Magneto-silica nanoparticles (MagSiNs) for combinatorial chemotherapeutics and gene delivery against metastatic cancers
We intend to target non-targetable cancer cells by tuning the magnetic field-induced force exerted by label-free magnetic nanomaterials at the cell membrane to selectively permeabilize the more compliant cancer cell membranes but not the stiff healthy cell membranes. Systemic delivery chemotherapeutics is toxic to all cells but more so to cancer cells due to the high metabolic rate of cancer cells. Targeted drug delivery using antibody tagged drug carriers reduces the dosage required to kill cancer cells and thereby mitigate the toxicity associated with systemic drug delivery. But the lack of unique targetable biomarkers on aggressive cancer cells such as 3º negative breast cancer makes the targeted drug delivery option a non-starter. But with the recent advances in biophysics, it is well documented that cancer cells have significantly different cell membrane stiffness in comparison to healthy cells. Cancer cell membranes are less stiff and more compliant, and the cells as a whole are easily deformable. The difference in membrane physical properties can be exploited by applying a force that is above the threshold required to permeabilize the cancer cells, but the force is still below the threshold required to permeabilize normal cells. While the cancer cell permeabilization and cancer cell-specific drug delivery have been validated in vitro, it is not known how effective such systems are in vivo. Studies that have tried to validate magnetic field directed drug delivery systems in vivo did so by sticking a permanent magnet on the tumor site before administering the nanocarriers intravenously or intratumorally. The requirement to know the tumor location beforehand to use magnetic targeting is the shortcoming of previous studies. As such, targeting modes offer no advantage over surgical re-sectioning, which is the current standard of care. Therefore, in this proposed study we will validate a label-free magnetic nanocarrier system (PEG-MagSiNs, PEG-Dox-MagSiNs) that will localize to cancer cells without the need for prior knowledge of the cancer cells’ location in vivo. We will exploit this property for selective drug-delivery and gene delivery to cancer cells. In this project the students will get exposure to (a) the conjugation of multiple therapeutics to PEG-MagSiNs; (b) design multiple modes of drug delivery from the PEG-MagSiNs (ON-demand, stimuli dependent, enzymatic release, etc.) and (c) execute in vitro cell and in vivo mouse studies that show selective targeting of PEG-MagSiNs to metastatic breast cancer cell and improved survivability in the sample group.
1. Chen Q1, Schweitzer D, Kane J, Davisson VJ, Helquist P. “Total synthesis of iejimalide B” J Org Chem. 2011 Jul 1;76(13):5157-69
2. Guduru, R.; Liang, P.; Runowicz, C.; Nair, M.; Atluri, V.; Khizroev, S., Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells. Scientific Reports 2013, 3, 2953
3. Nallathamby, P. D.; Hopf, J.; Irimata, L. E.; McGinnity, T. L.; Roeder, R. K., Preparation of fluorescent Au-SiO2 core-shell nanoparticles and nanorods with tunable silica shell thickness and surface modification for immunotargeting. Journal of Materials Chemistry B 2016, 4 (32), 5418-5428.
Project: Phononic nanoparticles for low-loss, tunable nanophotonics in the mid- and far-infrared
Phononic nanoparticles are a new class of optical materials with untapped potential for realizing new mid- and far-infrared detection and sensing nanotechnologies that are functionally analogous to ultraviolet and near-infrared plasmonic nanotechnologies but with even greater sensitivity. Phononic nanotechnologies have potential application in analytical chemistry, biomedicine, environmental science, homeland security, astrophysics, and geology. However, basic scientific knowledge of the governing structure-property relationships for engineering the optical properties of phononic nanoparticles are not well understood or developed. Therefore, students on this project will investigate the optical properties of candidate phononic materials using both modeling and experimental characterization of synthesized nanoparticles. As such, this interdisciplinary research experience will cut across both materials science and optical science.
Project: Scalable nanofabrication of metasurfaces using microsphere photolithography
Metasurfaces have shown dramatic potential to control radiation. However, the fabrication methods used for prototyping metasurfaces at visible and infrared wavelengths are cost prohibitive for most practical applications. Microsphere photolithography (MPL) uses a self-assembled microsphere array as an optical element to focus ultraviolet radiation to sub-diffraction limited photonic jets. Hierarchical structures can be produced by controlling the intensity of the incident illumination or its angular spectrum. This approach works well on non-planar substrates including optical fiber. The objective of this project is to use the MPL technique to create functional devices such as sensors and surfaces for controlling radiation heat transfer (e.g., daytime radiative cooling) depending on the student’s interest. The student will iteratively design the structure to perform the desired function, fabricate the device using microsphere photolithography, and characterize its performance using infrared spectroscopy. Other possible research projects could involve improving the fundamentals of the fabrication process. The project is multidisciplinary. Students with a background/interest in optics and/or microfabrication (physics, electrical engineering, mechanical engineering or chemistry) are encouraged to apply.
Project: Therapeutic cell engineering with synthetic nanoparticles
Professor Prakash Nallathamby • Aerospace & Mechanical Engineering, Bioengineering Graduate Program • 145 Multidisciplinary Research Building • 574-631-5735 • Prakash.D.Nallathamby.email@example.com
Endothelial colony forming cells (ECFCs) are a population of rare stem cells identified from circulating adult and human cord blood. Due to their robust clonal proliferative potential and ability to form de novo blood vessels in vivo, ECFCs have been used in pre-clinical and clinical studies as a therapeutic candidate to treat peripheral artery disease and critical limb ischemia. During the course of chronic diseases (e.g., cardiovascular diseases and diabetes) and aging, resident and circulating endothelial cells are subject to stress-induced premature dysfunction that limits their therapeutic use. The objective of this project is to utilize synthetic nanoparticle and surface cell engineering to improve the therapeutic potential of ECFCs. The student will synthesize and characterize nanoparticles, as well as quantify drug release. The student is expected to maintain the stem cell culture, and study cell-materials interaction using microscopy and molecular biology techniques. Students with a background in mechanical engineering, chemical/bio-engineering, material science, or biochemistry are encouraged to apply. Prior lab experience is preferred.
Project: Noble metal nanostructures for harsh environments
Material stability, be it photo, thermal, chemical, mechanical, or a combination thereof, is a ubiquitous subject of fundamental importance. It often decides whether a technology is viable, reliable, and sustainable and where the outcomes have economic, environmental, and social impacts. Noble metal nanostructures (e.g., Au, Ag, Pt, Pd) are functional materials that are used in numerous applications such as catalysis, energy, sensors, and optoelectronics. The tendency for such structures to morphologically reconfigure when heated can, however, disrupt or destroy the properties that were so carefully engineered in the first place and, in doing so, puts important applications (e.g., heat-assisted magnetic recording, high-temperature plasmonic sensing, solar thermophotovoltaics, and laser optics) at risk. With the understanding that temperature-induced shape changes originate from the diffusion of atoms, the goal of this project is to synthesize gold nanostructures with an oxide skeleton, where the skeleton’s purpose is to obstruct the most at-risk diffusion pathways so as to achieve a more stable configuration. The student working on this project will carry out various solution-based syntheses, characterize nanostructure properties, and test whether these properties can be maintained when the structures are exposed to heat treatments. Student applicants with a strong background in chemistry or materials science are preferred.
Project: Development of surface-enhanced Raman spectroscopy (SERS) substrates for operando spectroscopic characterization of gas separation membranes
The goal of this project is to develop new Surface-Enhanced Raman Spectroscopy (SERS) substrates that will be used as supports for gas separation membranes and will provide strong enhancement of the Raman signal intensity for characterizing the structure of the membrane in-situ under realistic operating conditions. The key feature of these new substrates is that they will have plasmonic gold nanoparticles incorporated into the polymeric material to enhance the Raman signal intensity. These substrates will enable new operando SERS measurements to be performed that will directly correlate the structure of polymeric gas separation membranes to their performance. The student will be responsible for synthesizing gold nanoparticles using wet chemistry techniques, depositing the gold nanoparticles onto a variety of porous polymeric substrates, characterizing the optical properties of the SERS substrates, depositing thin film polymeric membranes onto the SERS substrates, and, finally, performing SERS on the composite thin film structures. Laboratory experience, particularly in materials synthesis, is preferred though not required.
Project: Advanced functional near-infrared spectroscopy for use in real-world environments
Professor Joshua Koen • Psychology • 527 Corbett Hall • 574-631-9928 • firstname.lastname@example.org
In the past 25 years, noninvasive functional near-infrared spectroscopy (fNIRS) has been established as a valuable research tool in virtually all areas of basic and clinical human neuroscience: neurophysiology, development/behavioral/cognitive neuroscience, and neurology. However, due to fundamental physical constraints, most fNIRS imaging only captures a small portion of neurophotonic optical contrast indicative of brain physiology (i.e., slow hemodynamic changes), especially when designed for portability. This lack of specificity and accuracy prevents fNIRS from achieving its long-anticipated potential, e.g., robust brain-computer interfaces, clinical-grade diagnostics for acute brain injury and neural disorders, and as a tool for elucidating complex processes such as human neurovascular coupling. In this project, we are developing advanced wearable fNIRS systems with unprecedented depth sensitivity and accuracy based upon frequency domain diffuse optical spectroscopy for improving understanding of the human brain in real-world environments. Advanced wearable fNIRS could solve a long-standing limitation for neuroscience: understanding how the brain functions in real world, naturalistic environments. With these new tools, cognitive neuroscientists could break free of artificial, laboratory-constrained paradigms that can bias brain activity, limit studies of mobility, and prevent a full understanding of how the brain handles complex real-world scenarios and interacts with its environment. Depending upon the student’s background and interests, possible roles in this project include designing optoelectronic or embedded hardware systems, computational algorithm development, and assisting with human study data collection. Students with a background in electrical engineering, biomedical engineering, neuroscience, or related fields will be considered.
Project: Micromachining of high-speed, charge-sensitive scanning probe for studies of nanomaterials
a) Photograph of the SEBA on a SiNx membrane. The tip etch has been completed and all that remains is to glue it to the tuning fork and pop it out of the membrane. b) Zoom into the area with SEBA with a sharp tip visible. Insert shows the electron micrograph of individual single-electron boxes. c) A prototype probe mounted to a tuning fork of a low-temperature scanning atomic force microscope
We are developing a charge-sensitive scanning microscope to map charge distribution at the surface of quantum dots containing the so-called “Wigner crystals”– a curious phenomenon where electrons in the solid state are predicted to form spatial arrangements (e.g., triangular lattice). We place a tiny electronic device – “single-electron box array” (SEBA) very close to the tip of the scanning probe, which then flies a few nanometers away from the surface and senses the electron distribution in the sample. The electrical probing of the SEBA is done by using radio-frequency reflectometry enabling its fast and sensitive operation. The tiny chip containing SEBA needs to be glued to the tuning fork – an actuator that enables the scanning of our sensor in a very close proximity to the sensor. We demonstrated the electrical operation of the SEBA sensor, but now the challenge is to carefully carve out the chips containing SEBA from the substrate so they can be then attached to the tuning fork. It can be done using a smart combination of lithography and etching, and this will be the main target of the project. Once we meet this challenge, this unique probe can be transferred to the tuning fork and put to action. The student will work in the cleanroom on device fabrication, and on device measurements in the cryogenic nanoelectronics lab (B9 Stinson-Remick). Students studying electrical engineering, physics, mechanical engineering, or chemical engineering are preferred. Some knowledge of material science and electronics is helpful.
Project: Quantitative molecular imaging with photon-counting spectral computed tomography and nanoparticle contrast agents
X-ray imaging has been the primary means of imaging in clinical medicine, security screening, and non-destructive testing (NDT) for the last century. Radiography was revolutionized in the 1970s by the advent of three-dimensional computed tomography (CT), which has been continuously and incrementally improved to the present. However, a new revolution in CT is underway with the advent of photon-counting spectral CT, which enables multi-energy image acquisition for quantitative material decomposition of multiple materials and/or tissues within a single image data set. Quantitative molecular imaging of multiple, spatially coincident material compositions is not possible with other non-destructive molecular imaging modalities, such as conventional CT, nuclear imaging and magnetic resonance imaging, and will be transformative for diagnostic medical imaging, security screening, NDT, and as a research tool. Students on this project may investigate novel nanoparticle contrast agents that leverage the capabilities of spectral CT, and/or novel methods for combined image reconstruction and material decomposition that capitalize on data-rich spectral CT images. Students will utilize a prototype preclinical photon-counting spectral CT system, which is available only at Notre Dame and one other institution in North America.
Project: Polymers in next-generation rechargeable batteries
Advanced energy storage devices are sought after for use in electric vehicles and in conjunction with solar farms and wind farms for load leveling of the electric grid. To meet the cost and performance requirements of these applications, new battery chemistries are under development. Many of these battery designs incorporate functional organic components, such as polymer electrolytes, polymer coatings at the electrode-electrolyte interface, and polymer binders in the electrodes. In this project, the student will synthesize and characterize new organic materials for applications in rechargeable lithium or magnesium batteries. Multiple opportunities are available. Educational backgrounds in chemical engineering, chemistry, polymer science or engineering, and materials science or engineering are preferred.
1. J. Liu, P. D. Pickett, B. Park, S. P. Upadhyay, S. Orski, and J. L. Schaefer, “Non-solvating, side-chain polymer electrolytes as lithium single-ion conductors: synthesis and ion transport characterization,” Polymer Chemistry. http://doi.org/10.1039/C9PY01035A
2. H. O. Ford, L. C. Merrill, P. He, S. P. Upadhyay, and J. L. Schaefer, "Cross-Linked Ionomer Gel Separators for Polysulfide Shuttle Mitigation in Magnesium–Sulfur Batteries: Elucidation of Structure–Property Relationships," Macromolecules, 2018. (Cover) https://pubs.acs.org/doi/10.1021/acs.macromol.8b01717
Project: Adiabatic capacitive logic for ultra-low power electronics
Cross-section of MEMS ACL structure to be fabricated.
Anyone who owns a laptop knows that power dissipation and the associated heat are a problem for the microelectronics industry. As electronic devices scale down in size, they use less power (and hence energy), but is there a lower limit to the energy that must be dissipated by each device? Are there devices other than transistors that are able to dissipate less power. This project will investigate adiabatic capacitive logic (ACL), which uses variable capacitors used in pull-up and pull-down networks to form a voltage divider that can be used as a logic element. The variable capacitors will be built using micro-electro-mechanical structures (MEMS) to make nano-relay like devices. These devices map well onto adiabatic reversible computing approaches that can reduce power dissipation far below that possible with conventional approaches. The student will work in the cleanroom on device fabrication, and on device measurement. Students in electrical engineering, physics, or computer science are preferred. Some knowledge of programming and soldering is helpful.
Project: Control theory of ecosystems
Evolutionary control has a long history starting with agricultural domestication and culminating into contemporary genome editing technologies. However, this history is largely limited to controlling individual species. We view ecological and biosocial networks as the new circuit board, and evolution as a manufacturing process capable of fabricating eco-machines. Evolutionary control promises terraforming worlds, degrading pollution, and manufacturing astonishing compounds. This is a theoretical / computational project that aims to establish an analytical framework to steer the evolution of multiple populations that strongly interact with one other. Specifically, we wish to theoretically understand how to manipulate the connectivity of networks representing ecological or biosocial webs, which range from bacterial biofilms to rainforests. The project particularly focuses on ecological control under noisy or incomplete knowledge of the existing interactions and population levels of species. The project requires mathematical and computational dexterity. Applicants are expected to be familiar with MATLAB, differential equations / dynamic systems, and linear algebra.
Project: Targeting therapeutics through supramolecular affinity
We are motivated to advance the practice of therapeutic nanotechnology by capturing several of the benefits of antibody targeting while avoiding some known complications. Antibodies are used for targeting due to high affinity and biological tissue-specificity. There are, however, downsides to antibody use in nanomedicine that could present issues in application moving forward: (i) Antibodies are fundamentally opsonins, a bio-recognizable signal that promotes cell-mediated uptake and clearance of foreign particles (e.g., viruses) by the reticuloendothelial system. Can we use alternative high-affinity targeting groups that would not be subjected to active biological clearance? (ii) A typical therapeutic nanoparticle (diameter ~50-100 nm) endowed with antibodies (hydrodynamic diameter of ~10 nm) would be expected to have its surface properties and function altered by addition of this bulky appendage; furthermore, there is limited area on the nanoparticle surface to attach such a large targeting group. Can we design targeting based on minimal groups that have comparable affinity while limiting impact on the properties of the functional nanoparticle? Using ultra-high affinity supramolecular interactions as a type of “molecular Velcro,” our group envisions a new therapeutic nanoparticle targeting axis built on minimal small molecule affinity motifs that serve as drivers of localization, in lieu of large targeting antibodies, while at the same time not sacrificing any affinity relative to an antibody-antigen interaction. An undergraduate working on this project will be expected to learn techniques for formulating synthetic nanoparticles to contain drugs and quantifying drug release using a combination of spectroscopy and chromatography. Additionally, this individual will be tasked with validating this mechanism for targeting in vitro through microscopy of fluorescent nanoparticles on cultured cells. Students in chemistry, chemical engineering, materials science, or bioengineering are encouraged to apply. A minimum of some prior laboratory coursework is expected.
Project: Effects of acidity and salinity on polymer drug-delivery complexes
A host of interesting phenomena, both biological and technological, involve the complexation of charged polymers; these may be long polymers with well-defined secondary structure, such as proteins1, linear polyelectrolytes, or multi-branched species2. A particularly interesting phenomenon within polyelectrolyte solutions is coacervation3,4, a liquid-liquid phase separation where polymer-enriched liquid droplets are formed within a dilute phase5. Coacervation is an intriguing process where two primarily aqueous phases become immiscible6. Coacervates occur in many natural systems7,8, and have found application in microencapsulation9,10 and extraction11 processes, as their ultra-low surface tension allows them to readily assimilate nanoparticles or drug payloads within aqueous suspension. Complex coacervation, where two oppositely charged polymers make up the aggregate phase, is intimately related to the process of layer-by-layer deposition, where films up to micrometers in thickness are built by iterative surface adsorption of polyelectrolytes. Such films are of interest as solid electrolytes in lightweight batteries12,13, fuel-cell electrodes12,14, protective coatings14, and drug micro-encapsulation15. This topic inspires undergraduate projects involving characterization of coacervates through molecular dynamics simulation. These are focused on the use of complex coacervates in the delivery of therapeutic compounds to specific biological targets, as the highly charged, condensed environments they facilitate can act to stabilize and protect molecular and macromolecular species.
1. Liquid-liquid phase separation is prominent in biological environments, driven by the association of biopolymers such as proteins and nucleic acids. One project will involve exploring the role of various molecular driving forces, including charge interactions, molecular multipoles, hydrogen bonding, and dispersion forces in controlling the association of these molecules.
2. A second possible project involves the influence of the highly charged environment provided by a complex coacervate in stabilizing drug molecules--in particular protein based therapies--against deactivation and degradation. The student will explicitly determine how these environments shift a model drug's pKa and how the native structure of therapeutic compounds is modified using either coarse-grained or fully atomistic models. It is preferable (but not required) for students interested in this project to have prior experience with writing computer code (C++ preferred) and with scripting languages such as python and bash to facilitate running computations on the Whitmer group cluster and CRC machines.
1. S. L. Perry, L. Leon, K. Q. Hoffmann, et al. "Chirality-selected phase behaviour in ionic polypeptide complexes." Nature Communications, 6, 2015.
2. D. Priftis, X. Xia, K. O. Margossian, et al. "Ternary, tunable polyelectrolyte complex fluids driven by complex coacervation." Macromolecules, 47(9):3076-3085, 2014.
3. S. L. Turgeon, C. Schmitt, and C. Sanchez. "Protein-polysaccharide complexes and coacervates." Curr. Opin. Colloid Interface Sci., 12(4-5):166-178, 2007.
4. J. R. Nixon, A. H. Khalil, and J. E. Carless. "Phase relationships in the simple coacervating system isoelectric gelatin: Ethanol : Water." J. Pharm. Pharmac., 18:409-416, 1966.
5. D. Priftis and M. Tirrell. "Phase behaviour and complex coacervation of aqueous polypeptide solutions." Soft Matter, 8(36):9396, 2012.
6. F. M. Menger and B. M. Sykes. "Anatomy of a coacervate." Langmuir, 14(15):4131-4137, 1998.
7. N. Pawar and H. B. Bohidar. "Statistical thermodynamics of liquid-liquid phase separation in ternary systems during complex coacervation." Phys. Rev. E, 82(3):36107, 2010.
8. A. E. Smith, F. T. Bellware, and J. J. Silver. "Formation of nucleic acid coacervates by dehydration and rehydration." Nature, 214(5092):1038-1040, 1967.
9. C. I. Onwulata. "Encapsulation of new active ingredients." Annu. Rev. Food. Sci. Technol., 3:183-202, 2012.
10. S. R. Bhatia, S. F. Khattak, and S. C. Roberts. "Polyelectrolytes for cell encapsulation." Curr. Opin. Colloid Interface Sci., 10(1-2):45-51, 2005.
11. F.-J. Ruiz, S. Rubio, and D. Perez-Bendito. "Water-induced coacervation of alkyl carboxylic acide reverse micelles: Phenomenon description and potential for the extraction of organic compounds." Anal. Chem., 79:7473-7484, 2007.
12. J. L. Lutkenhaus and P. T. Hammond. "Electrochemically enabled polyelectrolyte multilayer devices: from fuel cells to sensors." Soft Matter, 3(7):804, 2007.
13. D. M. DeLongchamp and P. T. Hammond. "Highly ion conductive poly(ethylene oxide)-based solid polymer electrolytes from hydrogen bonding layer-by-layer assembly." Langmuir, 20(13):5403-11, 2004.
14. P. R. Van Tassel. "Polyelectrolyte adsorption and layer-by-layer assembly: Electrochemical control." Curr. Opin. Colloid Interface Sci., 17(2):106-113, 2012.
15. D. B. Shenoy, A. A. Antipov, G. B. Sukhorukov, and H. Mohwald. "Layer-by-layer engineering of biocompatible, decomposable core-shell structures." Biomacromol., 4(2):265-72, 2003.
Project: Predicting material elastic responses from molecular simulations
Elastic materials exhibit a restoring force which opposes applied stress, resulting from a perturbation away from thermodynamic equilibrium. Materials may exhibit different types of elasticity depending on their character.1 Each opposed deformation defines an elastic modulus; liquid crystals may have three or more elastic moduli characterizing their response to curvature deformations in their ordering field;2 solids, both crystalline and amorphous, also have several elastic moduli, such as the bulk modulus, shear modulus and Young's modulus. Each of these moduli may be related to derivatives of the system's free energy relative to a variable characterizing the extent of deformation. The Whitmer group has three potential projects related to measurements of elastic properties in silico, which build on recent formalisms3-5 utilizing free energy perturbation simulations to extract the elastic coefficients of liquid crystals into the domain of two-dimensional membranes and three-dimensional solids. We aim to characterize the typical elastic properties of each phase, and validate our data against previous simulations and theoretical models. Potential projects available in the Whitmer Group include:
- The utilization of recently developed coarse-grained models of biological membranes to understand how the enthalpic interactions and entropic packing alter the elastic behavior of a membrane. This project also seeks to demonstrate the effectiveness of "at-histogram" methods6 relative to fluctuation methods in determining surface tension and elasticity of membranes.
- Exploration of the phase behavior of ionic liquid crystals, salt species which self-assemble into phases with charged and uncharged domains. These have recently been of interest as novel battery electrolytes, whose performance is linked to their thermodynamics and the phases formed by individual molecules. Here we will examine the response behavior of self-assembled phases in the ionic liquid crystal [C16mim][PF6] using molecular simulations based on the polarizable AMOEBA force field, to understand the fundamental influence of polarization effects on the phases formed by these molecules and the resulting charge transport characteristics.
- Application of advanced sampling molecular dynamics to study the solid elastic constants of porous molecular crystals using free energy perturbation techniques. This work has widespread applicability to determine the thermodynamic and mechanical stability of self-assembled structures.
During the summer project, the student will work intensively on molecular simulation models and learn techniques of advanced sampling, in particular at-histogram methods6 used for the measurement of free energies. The student will be expected to have some familiarity with writing computer codes, preferably in C++. Knowledge of undergraduate thermodynamics (any of the subjects engineering thermodynamics, physical chemistry, or statistical mechanics are good starting points). Beyond this, only general knowledge of physics and chemistry is required.
1. Landau, Lev D. and Lifshitz, E. M., Theory of Elasticity, volume 7, (Elsevier New York 1986), 3 edition.
2. P. G. de Gennes and Prost, J., The Physics of Liquid Crystals, volume 4, (Oxford university press 1994), second edition, doi:10.1080/13583149408628646.
3. Joshi, Abhijeet A., Whitmer, Jonathan K., Guzman, Orlando, Abbott, Nicholas L., and de Pablo, Juan J., "Measuring liquid crystal elastic constants with free energy perturbations." Soft Matt., 10, 882-93 (2014), doi:10.1039/c3sm51919h.
4. Whitmer, Jonathan K., Chiu, Chi-cheng, Joshi, Abhijeet A, and de Pablo, Juan J., "Basis Function Sampling: A New Paradigm for Material Property Computations." submitted (2014).
5. Sidky, Hythem and Whitmer, Jonathan K., "Elastic properties of common GayBerne nematogens from density of states (DOS) simulations." Liquid Crystals, 0, 1-15 (0), doi:10.1080/02678292.2016.1201869.
6. Singh, Sadanand, Chopra, Manan, and de Pablo, Juan J, "Density of states-based molecular simulations." Ann. Rev. Chem. Biochem. Eng., 3, 369-94 (2012), doi:10.1146/annurevchembioeng-062011-081032.