Half of the world’s population is at risk for malaria, yet 90% of deaths due to malaria occur in sub-Saharan Africa, with the highest mortality rates occurring in children under 5. Due to this high mortality rate, children with common flu-like symptoms are often treated for malaria presumptively. This overtreatment with anti-malarial drugs can contribute to the emergence of drug resistant species. Commercially available diagnostic tools, such as blood smear microscopy and rapid diagnostic tests, offer greater specificity than presumptive diagnosis, but require the collection of a finger prick blood sample for diagnosis, generating biohazards and requiring consumables. This thesis introduces a new diagnostic concept to detect parasitized blood cells as they circulate in vivo, avoiding the requirement for blood collection. The work presented here investigates two major components of this concept: 1) develop and characterize a needle-free malaria diagnostic system, and 2) evaluate the performance of the system in biological environments of progressively increasing complexity. Results show promising optical signatures from two biomarkers for malaria detection. This work demonstrates the feasibility for imaging circulating blood cells in vivo through a non-invasive technique, warranting future investigations in a small malaria-infected sample population.