Medical diagnostic device development has been, in recent history, focused largely on paper-based diagnostics. Such devices offer incredibly low per patient cost with the downside of poor sensitivity and minimal ability to multiplex, or detect many different compounds simultaneously. New technologies which leverage exceedingly efficient silicon manufacturing have the potential to approach the cost of paper diagnostics with increased sensitivity and extensive multiplexing. This project aims to develop one such technology, silicon photonics. Using existing manufacturing technologies, silicon photonic sensing measures analyte mass accumulation through dielectric shift by taking advantage of the evanescent field of electromagnetic radiation passed through a silicon wafer. Aided by unique binding chemistries, silicon photonic devices are capable of highly specific analyte detection. The current stage in this project is focused on developing tools, the most notable being a rapid prototyping setup for testing chip design. The setup automates the interaction of a variety of necessary hardware components including fluidic pumps, movable stages, a microscope, and an infrared laser. By using such a rapid prototyping setup, it is hoped that a chip design that is extremely condusive to medical diagnostics will be developed and brought to cost effective levels.

Active drug targeting involves a specific “lock and key” binding interaction, which enables drugs to be delivered exclusively to specific sites in the body thereby reducing the toxic side effects and improving the efficacy of the drug. However, the field of active-targeting lacks an efficient drug carrier. We are proposing to use a RAFT-based glycopolymer as a novel drug carrier. It is composed of three different types of monomers: 1) pyridal-disulfide methacrylate (PDSMA) for drug conjugation to the polymer through a disulfide bond, 2) hydroxyl propyl methacrylate (HPMA) to make the polymer biocompatible and soluble in the body, and 3) carbohydrate monomers that enable active-targeting through the specific carbohydrate-receptor interactions on outer cell membranes. Then the three monomers are polymerized together by reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting copolymers were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The polymer size is around 8.5 kDa with low polydisperisty (<1.1). The polymer composition is 5% PDSMA, 75% HPMA, and 20% carbohydrate. The bioactivity of these polymers has been tested by surface plasmon resonance (SPR). In order to test the binding specificity of the mannose copolymer to ConA, I tested two different copolymers that contained different carbohydrate monomers. One polymer contains mannose, which specifically interacts with ConA. On the other hand, galactose, a stereoisomer of mannose, does not bind to ConA as expected. These results are promising because the mannose copolymer demonstrates good bioactivity, even though it contains a lower composition of mannose. These RAFT-based glycopolymers provide insight into the design of future active-targeting drug delivery systems.

Silicon microring resonator biosensors utilize nanoscale light confinement to detect biomolecules in a real-time and label-free manner with high sensitivity. Detecting the presence of antibodies that bind human tissue and blood antigens is crucial in transplant and transfusion medicine, as mismatched products can impact the clinical outcome of the recipient. The focus of the current research is to improve data analysis methods to perform serologic analysis of human plasma using a silicon photonic chip. Microring resonator chips were prepared by physisorption of streptavidin followed by functionalization with biotin-conjugated histo-blood group antigens. Testing was performed using undiluted human plasma to detect histo-blood group antibodies on the functionalized chip surface. A secondary enhancement step using an anti-immunoglobulin antibody enabled the quantification of the surface bound antibodies. Data analysis was performed using on-chip positive and negative controls, and kinetic analysis was accomplished using association models. The quantitative determination of antibody binding profiles with a model antibody system is discussed to show how these devices can ascertain kinetic behavior. Positive determination of plasma antibody content is shown, proving these devices can be used in this application at current clinical standards. These devices are suited for clinical translation and with proper quantitative models and testing they could surpass current clinical methods.

This project’s goal is producing microporous scaffold for tissue growth. These scaffolds are made out of crosslinked 2-hydroxyethyl methacrylate (HEMA), a hydrogel. They are formed by polymerizing the HEMA around polymethyl methacrylate (PMMA) beads that are of a constrained and predetermined size. The PMMA is washed away and we’re left with a porous scaffold of precise pore size. These scaffolds are used to encourage tissue growth and reduce inflammation and the foreign body reaction. The purpose of my research is to investigate blood vessel penetration into scaffolds by producing the largest sized scaffolds I can using novel techniques. We are currently limited to tissue scaffolds of a maximum thickness of 1 mm using our current techniques. With a larger thickness, our scaffolds could be used for many more applications that are presently unavailable with a thin scaffold. Our methods are varied and include creating multiple mold designs, polymerizing techniques, and chemical washing techniques. Once I can create these larger scaffolds we will test them in vivo to evaluate the foreign body reaction as well as angiogenesis in the region. There is a large range of possible future applications for these scaffolds. They could be tuned to encourage many different types of tissue growth.