Multifunctional Polydopamine Nanomaterials for Biomedical and Environmental Applications

Polydopamine (PDA), a synthetic and organic material, has emerged as a promising materialplatform for various applications in energy, environmental, and biomedical fields. PDA, formed by self-polymerization of dopamine, is rich in catechol and amine groups, which facilitate covalent conjugation and/or other non-covalent interactions with organic and inorganic materials. It is highly biocompatible, biodegradable, has broadband light absorption spectrum and excellent light-to-heat conversion efficiency. Also, it is easy to synthesize and functionalize. The combination of excellent characteristics of polydopamine-based nanomaterials, make them a promising adsorbent agent for environmental wastewater treatment and photothermal agent for biomedical applications. In the first half of thesis, we utilize the surface chemical functionality of polydopamine nanoparticles and their affinity to heavy metal ions and organic dyes to realize multifunctional filtration membranes that remove heavy metal ions and organic dyes from water through adsorption and catalytic degradation. Polydopamine exhibits high adsorption capacity toward heavy metal ions and organic dyes. Adsorption-based membrane technologies can be ideal for continuous flow water purification and have been extensively employed at industrial scale forxxiii water reclamation. By introducing polydopamine nanoparticles during bacteria-mediated cellulose growth, we fabricated a composite foam and membrane to study the adsorption behavior of the nanocomposites in different environmentally relevant pH and concentrations. The PDA/BNC membrane was used to investigate the removal efficiency of toxic heavy metals ions such as Pb (II) and Cd (II) and organic pollutants such as rhodamine 6G and methylene blue. Furthermore, to improve the range of pH in which the composite membrane is effective for dye removal, we fabricated another novel polydopamine/nanocellulose membrane, which is decorated with palladium (Pd) nanoparticles to remove organic dyes from contaminated water through catalytic dye degradation. In the second part of thesis, we develop polydopamine-based nanomaterials and experimental setups to be used in biomedical applications such as drug delivery and photothermal stimulation of cells. Using mesoporous silica-coated PDA nanoparticles as drug carrier and tetradecanol (TD) as gate keeper, we demonstrated that we could enhance the immune system response toward Melanoma cancer in mouse model through combination of photothermal and immunotherapy. Polydopamine core works as a photothermal agent to cause localized release of gardiquimod and tumor cell death upon NIR laser irradiation, hence, release of tumor associated antigens. Antigen presenting cells (APCs) including the dendritic cells and macrophages uptake these antigens and be activated around tumor site in response to these signals. Furthermore, these activated APCs, present the antigen to CD8+ cytotoxic T cells to actuate anti-tumor immune response. We have shown that this treatment is effective in reducing the tumor size and eliminating it in majority of cases. Also, the treatment created a memory effect in immune system toward melanoma cancer when second cancer event happened in mice that were treated before. Finally, we investigated the possibility of controlling the excitable cells’ activity through nanoheating. This was made possible by using polydopamine nanoparticles to localize the heat on cell membrane. We demonstrated that by using polydopamine nanoparticle and polydopamine/collagen 3D foam, and by applying NIR laser light, we can reversibly modulate the activity of in vitro cultured neurons and cardiomyocytes. A reduction in firing rate of neurons and an increase in beating rate of cardiomyocytes with different degree of inhibition and excitation was observed. Effect of different parameters on the quality of modulation was investigated

Experimental and Computational Study of Gas Bubble Removal in a Microfluidic System Using Nanofibrous Membranes

This paper presents a simple and efficient method for removing gas bubbles from a microfluidic system. This bubble removal system uses a T-junction configuration to generate gas bubbles within a water-filled microchannel. The generated bubbles are then transported to a bubble removal region and vented through a hydrophobic nanofibrous membrane. Four different hydrophobic Polytetrafluorethylene (PTFE) membranes with different pore sizes ranging from 0.45 to 3 μm are tested to study the effect of membrane structure on the system performance. The fluidic channel width is 500 μm and channel height ranges from 100 to 300 μm. Additionally, a 3D computational fluid dynamics (CFD) model is developed to simulate the bubble generation and its removal from a microfluidic system. Computational results are found to be in a good agreement with the experimental data. The effects of various geometrical and flow parameters on bubble removal capability of the system are studied. Furthermore, gas-liquid two-phase flow behaviors for both the complete and partial bubble removal cases are thoroughly investigated. The results indicate that the gas bubble removal rate increases with increasing the pore size and channel height but decreases with increasing the liquid flow rate

Bottom-Up Fabrication of Plasmonic Nanoantenna-Based High-throughput Multiplexing Biosensors for Ultrasensitive Detection of microRNAs Directly from Cancer Patients’ Plasma

There is an unmet need in clinical point-of-care (POC) cancer diagnostics for early state disease detection, which would greatly increase patient survival rates. Currently available analytical techniques for early stage cancer diagnosis do not meet the requirements for POC of a clinical setting. They are unable to provide the high demand of multiplexing, high-throughput, and ultrasensitive detection of biomarkers directly from low volume patient samples (“liquid biopsy”). To overcome these current technological bottle-necks, herein we present, for the first time, a bottom-up fabrication strategy to develop plasmonic nanoantenna-based sensors that utilize the unique localized surface plasmon resonance (LSPR) properties of chemically synthesized gold nanostructures, gold triangular nanoprisms (Au TNPs), gold nanorods (Au NRs), and gold spherical nanoparticles (Au SNPs). Our Au TNPs, NRs, and SNPs display refractive index unit (RIU) sensitivities of 318, 225, and 135 nm/RIU respectively. Based on the RIU results, we developed plasmonic nanoantenna-based multiplexing and high-throughput biosensors for the ultrasensitive assay of microRNAs. MicroRNAs are directly linked with cancer development, progression, and metastasis, thus they hold promise as next generation biomarkers for cancer diagnosis and prognosis. The developed biosensors are capable of assaying five different types of microRNAs at an attomolar detection limit. These sets of microRNAs include both oncogenic and tumor suppressor microRNAs. To demonstrate the efficiency as a POC cancer diagnostic tool, we analyzed the plasma of 20-bladder cancer patients without any sample processing steps. Importantly, our liquid biopsy-based biosensing approach is capable of differentiating healthy from early (“non-metastatic”) and late (“metastatic”) stage cancer with a p value <0.0001. Further, receiver operating characteristic analysis shows that our biosensing approach is highly specific, with an area under the curve of 1.0. Additionally, our plasmonic nanoantenna-based biosensors are regenerative, allowing multiple measurements using the same biosensors, which is essential in low- and middle-income countries. Taken together, our multiplexing and high-throughput biosensors have the unmatched potential to advance POC diagnostics and meet global needs for early stage detection of cancer and other diseases (e.g., infectious, autoimmune, and neurogenerative diseases)