Novel tools for malaria diagnosis, particularly rapid diagnostic tests (RDT’s), have provided alternatives to laboratory based microscopic disease confirmation. While RDT’s provide a disposable, low-cost option for parasite detection and some level of speciation, they fail to quantify parasitemia, which is useful in monitoring morbidity and identifying candidates for intensive treatment regimens. A low-cost microscope designed to gather quantitative parasitemia data from blood smears generated in microfluidic cartridges is presented. The system employs bi-modal imaging and uses components selected to optimize cost savings, system robustness, and optical performance. Bimodality is achieved by capturing two subsequent images for each field-of-view, with transmission-mode images providing cell counts and fluorescence-mode images providing biomarker localization data. A monochromatic LED for transmission illumination is employed with center wavelength aligned to the fluorophore label (acridine orange) emission peak near 520nm. Ray-trace models have been used to characterize performance while imaging in microfluidic cartridges with varying wall thicknesses. Results indicate that the necessary sub-micron resolution can be achieved using polymeric aspheres as critical optical components. System design and characterization results are presented from Zemax raytrace models, and imaging data from the prototype system are presented with correlations to modeled configurations. By optimizing the microscopy system to address a highly specific diagnostic gap, its complexity and cost can be reduced toward feasibility in the developing world while preserving utility as a potentially valuable tool to augment current malaria diagnosis and monitoring technologies.