BME PhD Prospectus Defense - Nga Ho

Starts:
2:00 pm on Monday, February 24, 2014
Ends:
8:00 pm on Sunday, February 23, 2014
Location:
8 St. Mary’s Street, Photonics Center, Room 339
Committee:
Prof. Muhammad Zaman (BME, Advisor - Chair)
Prof. James Galagan (BME)
Prof. Ahmad Khalil (BME)
Prof. Catherine Grgicak (School of Medicine)

Title: “Multiplexed, affordable, and portable platform for real time quantitative detection of substandard and counterfeit pharmaceuticals”

Abstract:
The World Health Organization estimates that about 10-30% of pharmaceuticals in the world are either substandard or counterfeit. The number is even higher in the developing countries. From a public health perspective, a key contributor to the development and proliferation drug resistant strains of infections, including TB, malaria and other infections that are leading killers in resource limited settings is poor quality medicines. Most of the main causes are the profit of the pharmaceuticals itself, the poor manufacture and quality control, and/or the inappropriate storage conditions. Poor quality drugs lead to loss of life, create morbidity, strain the financial structure of the health system and lead to long-term drug resistance that affects us all.
The current technology for screening poor quality drugs can be divided into 2 categories: the high end, precise and high cost technologies (such as High Performance Liquid Chromatography) and lower cost and qualitative technologies (such as Thin-Layered Chromatography). The high-end methods can give a precise measurement of active pharmaceutical ingredients (API) concentration and the presence of impurities in the tablets, but require trained personnel, advanced machine and lab set up, not suitable for field testing where most of poor quality pharmaceuticals have been found. The lower cost techniques require little training and simple equipment to operate at a relatively inexpensive price, but only gives qualitative results. In addition, most of current methods do not look at the dissolution profile of the tablets simultaneously with the concentration of API. Therefore, we propose to develop an assay that can quantify the concentrations of multiple APIs simultaneously and measure dissolution rates.
Our research proposal has three main parts in the assay development: 1) Novel chip design, 2) API detection probe design and 3) quantification and optimization. For proof-of-concept, an antimalarial drug (artesunate) and antibacterial antibiotics (sulfamethoxazole and trimethoprim) are selected to demonstrate the probe development and test the chip performance. We will carry out our research using the following three specific aims. The first aim is to validate antimalarial probes at different conditions, design a chip with incubation chamber that captures the luminescent signal from the reaction between the probes and API, and test the chip performance with samples from the field. The first part of the second aim focuses on setting up a systematic evolution of ligands by exponential enrichment (SELEX) for screening DNA sequences (aptamer) that binds specifically to trimethoprim. The second part is the development of a probe that reacts chemically with sulfamethoxazole to produce fluorescent signal and the comparison the small molecule and aptamer based methods. In the last aim, our goal is to design a chip that can measure 4 different concentration standard samples and a tablet sample for real time quantification and also does discrete solution curve at 5 different time points for 2 different APIs.
Overall, the assay will be rapid, robust, portable, inexpensive, multiplexed, quantitative, specific, and sensitive. Also, our new system will measure the API concentration directly with a standard curves and do discrete dissolution profile. At a big picture level, emphasizing drug quality and creating robust mechanisms of drug testing will improve health outcomes and enhance treatment efficacy in resource limited settings.