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 tuberculosis (TB), malaria and other infections that are leading killers in resource limited settings is poor quality medicines. Most of the main causes are profit driven corruption in many pharmaceutical companies, 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 ingredient (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. In order to address current gaps in knowledge, my research proposal has three main parts in the assay development: 1) Development of an fluorescent/luminescent assay for detection of counterfeit/substandard antimalarial using small-molecules-based methods and field testing in Ghana; 2) Development of a fluorescent assay for detection of water-soluble pharmaceuticals using SELEX; and 3) Design a detection platform using microfluidic chips for real time quantification of multiple active pharmaceutical ingredients. For proof-of-concept, an antimalarial drug (artesunate and amodiaquine) and antibacterial antibiotics (sulfamethoxazole and trimethoprim) are selected to demonstrate the probe development and test the chip performance. Overall, the assay will be rapid, robust, portable, inexpensive, multiplexed, quantitative, specific, and sensitive. 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.