Trihydroxybenzoic Acid Analogs as a Potential Drug Formulation for Inflammatory Diseases

The project seeks to establish the link between toll-like receptors (TLR) in the pathogenesis of inflammation and formulate a trihydroxy benzoic acid (THBA) analog as a potential drug formulation for inflammatory diseases. We aim to develop a stable drug-polymer complex of THBA using pH-sensitive polymers that will target inflammation. Various analogs of THBA will be synthesized with nano-co-precipitation experimentation for optimization using a variety of polymers, solvents, and stabilizers to increase the solubility in aqueous conditions and determine the most effective combination. The particle size, drug loading, and dissolution profile under various pH are discussed with various polymers. The formulated complex is solid and will be studied for biochemical, genetic changes in the human tissues in the class II environment. The physiological and pharmacological effects will be studied in live mice in an animal facility. Together the results will aid conclusively deduce the role of TLRs in the causation of inflammation, and efficacy of the drug. In the long term, this may reveal TLRs as druggable targets and the trihydroxy benzoic acid polymer complexes as an inhibitor of the TLRs respectively

Drug-loaded PLGAs for 3D printed wound-healing patches using DMSO as the solvent

Considering that skin is the most extensive organ in the human body, it comes as no surprise that it is so heavily involved in regulating and mediating most biological functions, such as providing a protective barrier against mechanical, thermal, and physical injury, regulating temperature and water balance, perceiving sensory information, and aiding the immune response to infections or other hazardous agents. For this research project, a particular interest is the skin’s potential as a drug delivery system, which can be optimized using smart technologies (e.g., medicated patches, wound dressings, and hydrogels). In fact, the delivery of drugs through the skin provides a convenient route of administration that is both non-invasive and self-administrable, and thus preferable to injections. Not only does this significantly reduce medical complications, but it also promotes patient compliance and the completion of treatment. By pairing the skin’s role as a drug delivery system with smart bio-inspired technologies, such as nanoengineering and 3-D printing, there is a wide range of potential biomedical applications. With the aim of advancing the field of wound-healing and personalized medicine, this research project was designed to test and optimize the synthesis of a PLGA/DMSO gel loaded with quercetin, a controlled-release drug. Trials allowed the identification of optimal PLGA types (85:15 and 90:10 PLGA, high molecular) for freezing and 3D-printing. These tests will inform a subsequent Ignite 22/23 project, which will 3D-print the PLGA/DMSO gel to fabricate wound-healing patches

Two photon polymerisation enabled plasmonic sensors for Inflammation monitoring

The rapid technical development of ultrashort laser systems is creating exciting possibilities for very precise localization of laser energy in time and space. A promising three-dimensional microfabrication two-photon polymerization method that has recently attracted considerable attention with ultrashort laser pulses. This method will be utilized to fabricate micropyramid with nano side slits for surface enhanced plasmonic interaction with incident light of a specific wavelength. When a biomolecule is close to LSPR region, the electrons and bonds vibrate energetically changing the impedance of the system.This impedance change will be measured for C-Ractive protein, an inflammation biomarker. The calibration curve with spiked CRP in PBS and plasma will be used to measure the unknown concentrations of CRP in real-life sample

Inflammation Monitoring by Two photon Polymerized Enhanced Surface Sensors

Prolong stay in space can have adverse side effects on human body. Various space flight stressors such as microgravity, isolation, confinement, radiation exposure and circadian shifts can impact the immune system drastically. One of the immune markers, interleukin-6 (IL-6), is shown to be elevated in blood when undergone these stressors. The research aims to develop an electrochemical impedance sensor to detect various concentration of IL-6 in saline solution by using surface enhancement methods on gold-coated pyramids fabricated using two-photon polymerization lithography (2PP). The biomolecules are attached to the gold coated pyramids enhanced surface area and are excited with 520 nm laser. The change in surface characteristic due to the attachment of biomolecule and the excitation is measure through impedance analyzer. The range of concentrations of IL-6 to be detected through these methods are from 1 pg/ml to 1µg/ml

Highly Stretchable, Room Temperature Self-Healing Polymer via Crosslinking and Intermolecular Network for Applications in Aerospace and Robotics

Keywords: Polymer, Self-Healing, Room temperature, Flexible, Electronics Self-healing materials have gained significant attention due to their efficient ability to intrinsically heal without the use of external human intervention. Several mechanisms for repair within self-healing materials can be found, such as catalyst containing micro beads, healing from an external energy source such as ultraviolet light or heat, and supramolecular network bonding. However, many of these techniques remain challenged due to their lack of mechanical strength, faulty energy diffusion, and poor self-healing ability within limited time. In the given project, a material with efficient self-healing ability at room temperature and high mechanical strength is exemplified. The self-healing material utilizes a soft poly(oxy-1,4-butanediyl) (PTMEG) backbone that limits monomer clumping and microphase separation. Furthermore, the dual hydrogen bonding and high crosslinking monomer allows for excessive mechanical strength, while the weak single hydrogen bonding subunit creates mechanical strain diffusion by forming a diverse supramolecular network of temporary intermolecular bonds. Varying ratios of TDI and IP are tested in conjunction with 1000MW and 2900MW PTMEG backbones to exemplify varying degrees of self-healing and mechanically strength abilities for materials with applications in dielectric applicators, biosensing, and various self-healing electronics. The characterization of the polymer was accomplished using Fourier-transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The self-healing property was characterized by producing small slices in the material in both an aqueous and air environment at room temperature

Dielectrophoresis-Assisted Pathogen Detection on Vertically Aligned Carbon Nanofibers Arrays in a Microfluidic Device

In this chapter, we focus on utilizing nanoelectrode arrays fabricated with vertically carbon nanofibers (VACNFs) for pathogen detection based on a “point-and-lid” dielectrophoretic device in a microfluidic channel. This technique is utilized to concentrate particles from the bulk flow and detect pathogens based on fluorescence, surface-enhanced Raman spectroscopy (SERS) and impedance measurements. The advantage of VACNFs is their ultrasmall diameter (~100 nm) and the high aspect ratio (50:1). When coupled with a macroscopic indium tin oxide (ITO) electrode, it produces a large electric field gradient (∇E2 = ~1019 − 1020 V2 m−3) which is harnessed for pathogen detection based on dielectrophoresis. Several noninfectious pathogens including bacteria Escherichia coli DHα5, inactivated vaccinia virus (species: Copenhagen strain, VC-2), and Bacteriophage T4r were utilized as model species to study the size effect and kinetics of dielectrophoretic capture in this study. The comparable size of the nanoelectrode produced strong interaction with virus particles, generating striking lightning capture patterns and high detection sensitivity. The dielectrophoretic capture at the nanoelectrode arrays is successfully integrated with a portable Raman probe as a microfluidic chip for ultrasensitive detection of bacteria E. coli DHα5 using SERS-tagged gold nanoparticles co-functionalized with specific antibodies

Phenolic Acid Analogues as a Potential Drug Formulation for Inflammatory Diseases

Phenolic Acid Analogs as a Potential Drug Formulation for Inflammatory Diseases: We seek to establish the link between toll-like receptors (TLR) in the pathogenesis of inflammation and formulate a phenolic acid analog as a potential drug formulation for inflammatory diseases. We developed a stable drug-polymer complex of a phenolic acid using pH-sensitive polymers that will target inflammation. Various analogs were synthesized with nano-co-precipitation experimentation. Using a variety of polymers, solvents, and stabilizers the most effective combination for optimal delivery was determined. The particle size, drug loading, and dissolution profile under various pH are identified with various polymers. The formulated complex will be studied for biochemical, genetic changes in the human tissues in the class II environment. The physiological and pharmacological effects will be studied in live mice in an animal facility. These results will broaden the understanding and deduce the role that TLRs have in the causation of inflammation, and efficacy of the drug. In the long term, this may reveal TLRs as druggable targets and the phenolic acid polymer complexes as an inhibitor of the TLRs respectively. Specifically, this project aims to explore the effect of this stable drug-polymer complex on Inflammatory Bowel Disease, which affects 15% of American primary care patients. Currently, all pharmaceutical solutions pose negative side effects and the drug utilized in this complex will prospectively reduce these effects

Review of the Statistical Analytical Techniques for the Optimization of Ultrahigh Pressure for Extracting Biologically Active Compounds

Biologically Active Compounds (BACs) are organic compounds that are rich in nutrients and have characteristics such as anti-hypertensive, anti-cancer, and antioxidant properties. When compared to conventional extraction methods, such as Soxhlet extraction, percolation, maceration, it takes a longer amount of time, resulting in lower percent yields, and the BACs are exposed to higher temperatures which might cause damage to the BACs when extracted. This review includes the factors that researchers have looked at are: temperature, pressure, the solvent to pomace ratio, and solvent effects which will allow us to better analyze the % yield of BACs extracted and optimize the procedure. The focus of this project is to review the statistical methods for studying the technique of ultra-high-pressure extraction of BACs from pomace (food waste). In conclusion, the multivariate statistic technique such as response surface methodology (RSM), has advantages to classical one-variable-a-time optimization, such as the generation of large amounts of information from a small number of experiments and the possibility of evaluating the interaction effect between the variables on the response

Development of a Flexible, Room Temperature Self-Healing Polymer via Reversible Hydrogen Bond Network

Self-healing polymers are attractive materials with the ability to intrinsically or extrinsically heal without the use of external human intervention. Several mechanisms for repair within self-healing materials can be found, such as catalyst containing micro beads, healing from an external energy source such as ultraviolet light or heat, and supramolecular network bonding. However, many of these techniques remain challenged due to their lack of mechanical strength, faulty energy diffusion, and poor self-healing ability within limited time. In the given project, a material with efficient self-healing ability at room temperature and high mechanical strength is exemplified. The self-healing material utilizes a soft poly(oxy-1,4-butanediyl) (PTMEG) backbone that limits monomer clumping and microphase separation. Furthermore, the dual hydrogen bonding and high crosslinking monomer allows for excessive mechanical strength, while the weak single hydrogen bonding subunit creates mechanical strain diffusion by forming a diverse supramolecular network of temporary intermolecular bonds. Varying ratios of TDI and IP are tested in conjunction with 1000MW and 2900MW PTMEG backbones to exemplify varying degrees of self-healing and mechanically strength abilities for materials with applications in dielectric actuators, biosensing, and various self-healing electronics. The self-healing property was characterized by producing small slices in the material in both an aqueous and air environment at room temperature. The characterization of the polymer was accomplished using Fourier-transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC)

Detection of extremely low concentration waterborne pathogen using a multiplexing self-referencing SERS microfluidic biosensor

Citation: Wang, C., Madiyar, F., Yu, C. X., & Li, J. (2017). Detection of extremely low concentration waterborne pathogen using a multiplexing self-referencing SERS microfluidic biosensor. Journal of Biological Engineering, 11, 11. doi:10.1186/s13036-017-0051-xBackground: It is challenging to achieve ultrasensitive and selective detection of waterborne pathogens at extremely low levels (i.e., single cell/mL) using conventional methods. Even with molecular methods such as ELISA or PCR, multi-enrichment steps are needed which are labor and cost intensive. In this study, we incorporated nano-dielectrophoretic microfluidic device with Surface enhanced Raman scattering (SERS) technique to build a novel portable biosensor for easy detection and characterization of Escherichia coli O157:H7 at high sensitivity level (single cell/mL). Results: A multiplexing dual recognition SERS scheme was developed to achieve one-step target detection without the need to separate target-bound probes from unbound ones. With three different SERS-tagged molecular probes targeting different epitopes of the same pathogen being deployed simultaneously, detection of pathogen targets was achieved at single cell level with sub-species specificity that has not been reported before in single-step pathogen detection. Conclusion: The self-referencing protocol implements with a Nano-dielectrophoretic microfluidic device potentially can become an easy-to-use, field-deployable spectroscopic sensor for onsite detection of pathogenic microorganisms