Glioblastomas (GBMs) are malignant brain tumors associated with lethal cancers that have a great tendency to rapidly invade healthy brain tissue, leaving patients with short survival times and decreased quality of life. The median survival time for patients treated with the chemotherapeutic, temozolomide (TMZ), and radiation therapy is around 12 months, and many patients develop resistance to TMZ due to high activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repairing protein. However, the inclusion of an MGMT inhibitor, such as O6-benzylguanosine (BGS), could work to combat this problem. Currently, the Zhang lab is working on creating nanoparticles (NP) with drug-delivery capabilities, which can cross the blood-brain barrier and deliver chemotherapeutics to targeted glioma cells. This highly drug loaded NP model (IOPH-pBGS) efficiently inhibits MGMT and sensitizes GBM cells to TMZ. However, we wanted to know to what extent a targeting agent would improve this model, and how much efficacy can be increased through optimization of the targeting agent conjugation process. We hypothesized that we can significantly increase drug delivery to tumors by avoiding nonspecific uptake of NPs in healthy cells. My research project was to optimize chlorotoxin (CTX) conjugation to the NPs for use against GBMs. CTX is a small amino-acid peptide sequence that has the ability to target GBM cells. We optimized: the point in the NP synthesis process to add CTX, the length of polyethylene glycol linker to attach CTX to the NP surface, and the reaction ratio of CTX to NP in order to optimize both drug loading and targeting efficacy. In order to evaluate the effectiveness of the various CTX conjugated NPs, SDS-PAGE peptide quantitation assays, cell targeting assays, MGMT quantitation assays and clonogenic cell survival assays were utilized.

Sodium-yttrium-fluoride (NaYF₄) upconverting nanocrystals are currently being investigated for their applications in bioimaging, color displays, solar cells, and photocatalysis. Recently, Yb³⁺-doped-NaYF₄ nanoparticles have been predicted to also be a promising host material for laser refrigeration applications. However, to date, the laser-refrigeration of β-NaYF₄ single-crystals has not been reported due to challenges in bulk Czochralski crystal growth. We have demonstrated laser refrigeration of hydrothermally synthesized β-NaYF₄ nanowires for the first time. With a low cost, scalable hydrothermal synthesis process, we can prepare different sizes, morphologies, and phases of NaYF₄ nanoparticles by tuning the initial reagent concentration, synthesis time, and temperature. In the future, our results can be used to synthesize the optimal NaYF₄ nanowires for localized optoelectronic device cooling and physiological laser refrigeration.

Paclitaxel (PTX) is one of the most commonly applied chemotherapeutic drugs to treat cancers. PTX inhibits mitotic spindle assembly and chromosome segregation so that cancer cells cannot proliferate normally. While highly effective in arresting cancer development, PTX is extremely hydrophobic and insoluble in physiological environment. Hence loading PTX onto a bio-compatible and water soluble drug carrier is important. Here we report a nanoparticle formulation that can effectively load and stabilize PTX, and transport it into cells. To synthesize the nanoparticle drug delivery systems, iron oxide nanoparticles were first nucleated, grew and capped with oleic acid to form oleic acid coated iron oxide nanoparticles (IONP-OA). Amphiphilic triblock copolymer hexanoyl-chitosan-PEG (CP6C) was made by attaching methoxy polyethylene glycol and hexanoic anhydride to chitosan backbone. CP6C was coated onto IONP-OA through hydrophobic interaction between oleic acid and hexanoyl groups. PTX was loaded in the hydrophobic region between the two groups. Then, chlorotoxin (CTX) as the targeting ligand for brain tumor was conjugated onto nanoparticle through a heterobifunctional linker. The desired product structure (CTX-PTX-NP) was confirmed by TEM, FT-IR and 1H NMR. Characteristic FT-IR and 1H NMR peaks of hexanoyl and mPEG were observed. The product nanoparticles were stable in size (~50 nm) after a 4-week incubation. Importantly, the PTX loading efficiency was 31.3% PTX/Fe weight to weight ratio determined by HPLC and ferrozine assay. The product showed only minimum drug leak in aqueous solution, indicating that the hydrophobic drug was successfully encapsulated and stabilized in nanoparticle. Furthermore, when applied to glioma cells U118MG, the nanoparticles showed robust cellular uptake and were able to inhibit 80% cell growth in vitro. In summary, our nanoparticle can successfully load hydrophobic drug PTX and delivery it into glioma cells effectively.

Anodized aluminum oxide (AAO) with macroscopically-aligned, hexagonally-packed nanopores is an attractive substrate both for making nanomaterial templates and forming membranes. AAO has a tunable pore diameter, a well-defined pore structure, and is easily scalable. However, it is brittle which makes it difficult to work with and limits its applications. Here we present a method for synthesizing AAO nanoporous membranes that are flexible. We perform a two-step anodizing process using 99.999% pure aluminum foil in Oxalic acid. We make flexible AAO by patterning aluminum seams in a triangular grid to relieve stress. Additionally, fittings and a patterned gasket protect the aluminum strips from the anodizing solution. With flexible AAO, further research can be carried out on pharmaceutical separation applications and biochemical filtration. For this project I wrote up a protocol for my laboratory to make AAO on site for use in future research projects.

A dynamic membrane system with nanometer-thick electrodes is able to selectively bind genetically modified proteins with specific protein ligands and pump them across the membrane with sequential voltage pulses. The previous tests on this system show that after several separations of mixed proteins, the separation rate decreases due to biofouling; non-specific proteins lie on the surface of membrane and diminish the ligand’s affinity to target modified proteins. A colayer of non-fouling zwitterionic peptides and affinity ligands is functionalized to the membrane surface.We set up rubber chambers to mimic the working environment of the seperation system. Mixed protein separations are performed  in the chambers and permeates are quantified with UV-Vis spectroscopy. After introducing the zwitterionic non-fouling agent, the membrane maintains constant separation rates while retaining high binding capacity.

Single-junction solar cells that employ metal-halide perovskites have generated intense interest due to their rapid increase in demonstrated power conversion efficiency. In contrast with previously explored solar cell active materials, perovskites are solution-processable, tunable band-gap materials with small energetic losses. Because of this they are ideal candidates for use in tandem solar cells, which integrate a large-bandgap and a small-bandgap solar cell into one structure, significantly increasing maximum efficiency. Current tandem solar cells can have marked efficiency loss due to excess window layers and poor layer design leading to absorptive losses. Additionally, the comparatively poor understanding of perovskite processing methodology can result in suboptimal perovskite active layers. Our goal was to explore the feasibility of using a metal grid-type electrode collection layer in place of a standard transparent window layer, in order to minimize absorptive losses for successful integration into a tandem structure. Principally important to characterizing this structure was exploration of device fabrication and perovskite processing methods that resulted in effective carrier extraction. The mean diffusion length of charge carriers in a material is one of the primary factors that affect carrier extraction. Current literature gives a diffusion length ranging from 0.3 – 10 um for methylammonium lead iodide (MAPI) perovskite layers. We fabricated test cells with electrode grid pitches ranging from 0.4 – 10 um using photolithography techniques. We then explored the effect of variable deposition method, heat treatment and solution composition as well as observed layer morphology on diffusion length and charge extraction using photoluminescence spectroscopy.

Composite materials utilizing nanoparticles can exhibit improved properties and qualities. Silica (SiO₂) nanoparticles exhibit unique optical, electrical, and mechanical properties and are an ideal candidate for the dispersed phase in many applications, such as precursors for optical films with controlled optical properties and rheology. Atomic forces dominate when particles shrink to sizes below the visible wavelength spectrum, generating unique phenomena. One problematic phenomena, however, is the agglomeration of primary particles into a polydisperse collection of dimer, trimer, or larger secondary particles when calcined or mixed into the continuous phase of the composite. Monodisperse colloids and nanopowders are critical for consistent and optimized performance of composites and nano features. Silica particle synthesis has been well researched, but the practicality of producing pure, monodisperse, and non-agglomerated particles at scalable operations is still in question. This research investigates the factors leading to the agglomeration of spherical silica nanoparticles when synthesized with variations of the Stöber method, and evaluates changes in synthesis parameters that can reduce agglomeration in order to determine the most viable process for scalable production. Parameters that are manipulated include the ratio of ammonia catalyst with tetraethyl orthosilicate (TEOS) in ethanol or methanol solvents and the addition of anionic electrolytes. SEM imaging is then used to evaluate the distribution of the particles. Surface treatments for anti-agglomeration as incorporated into the synthesis process or as post processing are also evaluated, with minimal remnant impurities in the product as a priority. The end goal of this research is to successfully synthesize monodisperse sub-10 nanometer silica particles for pseudoplastic shear-thinning precursors used in fast throughput nanoimprinting of an antireflective layer for solar cells.

 As the world looks for sources of clean energy, the recent advances in lead halide solar cells have shown great promise, increasing from 3% efficiency to 20% in the last few years. Many lead halide or perovskite devices provide the opportunity for low carbon solar cell manufacturing, yet they are still scaled to laboratory settings. By using additive solution based treatments, large-area high-efficiency solar films can be scalably processed through the rapid deposition of perovskite solvents onto roll to roll printers similar to the printing presses used in the newspaper industry. In order to allow for the scaling of the perovskite solar cells, areas of improvement are needed on the small scale with perovskite films on glass substrates, including the need for rapid thermal processing to reduce processing time from 30+ minutes to a matter of seconds. In our work, various methods of rapid thermal treatment on perovskite films were performed by using a xenon flash lamp under different experimental intensities and time series. The flash lamp uses high pulses of energy that interact with the film to rapidly heat it while avoiding degradation due to quick thermal dissipation. These samples will be characterized using X-ray Diffraction, UV-Vis Spectrometry, and Scanning Electron Microscope in order to examine the degradation and grain growth effects. Then, the results will be compared to samples thermally treated from 10 minutes to an hour. Future work of this heat treatment process will be used to optimize the rapid thermal processing needed to roll coat scalable perovskite solar cells films onto a flexible plastic substrate, polyethylene terephthalate (PET). The xenon flash lamp will be attached to the roll to roll printer which will print large area flexible perovskite solar cells to reduce wasted processing energy, and meet increasing energy production needs.

In the last 10 years, perovskite solar cell efficiencies have increased from four to over twenty percent. Perovskite materials possess great application in thin-film photovoltaics and roll to roll processing. Unlike in traditional silicon solar cells with layer thicknesses on the order of 100 microns, the perovskite layer in a thin-film photovoltaic can be fewer than 100 nanometers. This study looks at the suitability of zinc oxide nanoparticles for use as an electron transport layer in a lead halide perovskite thin-film. Of particular interest is the ability to adjoin the zinc oxide and perovskite layers without any degradation of the perovskite. The effects of solvents, additives (i.e. surfactants), and particle size are analyzed using a variety of methods such as x-ray diffraction, transmission electron microscopy, and photoluminescence spectroscopy to determine optimal interfacial properties and exciton separation in the electron transportation layer. The success of the ZnO layer is further analyzed by comparing the quantum efficiencies and current-voltage characteristic curves of the assembled solar device to an identical solar cell that uses PCBM as the electron transport layer. PCBM is one of the most effective electron transport layers, but due to high cost, the need for alternatives such as ZnO was made necessary. The overall goal of this project is to attain efficient solar cells, using cost-effective materials and processing methods. By doing so, it will open up the field of solar energy for a wider market and broader applications.

Complications and mortality from glioblastoma multiforme (GBM) are often the result of tumor metastasis and thus, understanding the underlying mechanisms in glioma cell migration to help minimize tumor diffusion is of vital importance. Previously in our lab, aligned co-polymer blend chitosan-polycaprolactone (C-PCL) nanofibers have been shown to promote a migratory phenotype and an upregulation of invasion-related genes in GBM cells after 24 hours of culture. Here, we aim to further investigate the effects of nanofiber chemistry on the migratory and invasive character of GBM cells by coating C-PCL nanofibers with hyaluronic acid (HA), a major component of the brain extracellular matrix (ECM). Human U-87 MG GBM cells, a model glioma cell line, were used to study the GBM behavior on the nanofibers. Proliferation assays to determine the biocompatibility of the nanofiber platforms with and without HA were evaluated followed by cell morphology analysis to evaluate elongation and alignment. Overnight migration studies were conducted to determine if migration profiles on the nanofiber platforms were similar to those reported in vivo. Drug resistance and invasion-related genes were assessed to determine if culture on HA-coated C-PCL nanofibers could increase malignancy in GBM. Finally, flow cytometry was used to pinpoint the population of cells expressing a more invasive phenotype and thus provide an idea if HA-coated C-PCL nanofibers were a suitable in vitro platform for developing high-throughput anti-invasion cancer therapies.