A lab-on-chip for malaria diagnosis and surveillance.

BACKGROUND: Access to timely and accurate diagnostic tests has a significant impact in the management of diseases of global concern such as malaria. While molecular diagnostics satisfy this need effectively in developed countries, barriers in technology, reagent storage, cost and expertise have hampered the introduction of these methods in developing countries. In this study a simple, lab-on-chip PCR diagnostic was created for malaria that overcomes these challenges. METHODS: The platform consists of a disposable plastic chip and a low-cost, portable, real-time PCR machine. The chip contains a desiccated hydrogel with reagents needed for Plasmodium specific PCR. Chips can be stored at room temperature and used on demand by rehydrating the gel with unprocessed blood, avoiding the need for sample preparation. These chips were run on a custom-built instrument containing a Peltier element for thermal cycling and a laser/camera setup for amplicon detection. RESULTS: This diagnostic was capable of detecting all Plasmodium species with a limit of detection for Plasmodium falciparum of 2 parasites/µL of blood. This exceeds the sensitivity of microscopy, the current standard for diagnosis in the field, by ten to fifty-fold. In a blind panel of 188 patient samples from a hyper-endemic region of malaria transmission in Uganda, the diagnostic had high sensitivity (97.4%) and specificity (93.8%) versus conventional real-time PCR. The test also distinguished the two most prevalent malaria species in mixed infections, P. falciparum and Plasmodium vivax. A second blind panel of 38 patient samples was tested on a streamlined instrument with LED-based excitation, achieving a sensitivity of 96.7% and a specificity of 100%. CONCLUSIONS: These results describe the development of a lab-on-chip PCR diagnostic from initial concept to ready-for-manufacture design. This platform will be useful in front-line malaria diagnosis, elimination programmes, and clinical trials. Furthermore, test chips can be adapted to detect other pathogens for a differential diagnosis in the field. The flexibility, reliability, and robustness of this technology hold much promise for its use as a novel molecular diagnostic platform in developing countries.

Maturation of hemispheric specialization for face encoding during infancy and toddlerhood.

Little is known about the neural processes associated with attending to social stimuli during infancy and toddlerhood. Using infant magnetoencephalography (MEG), fusiform gyrus (FFG) activity while processing Face and Non-Face stimuli was examined in 46 typically developing infants 3 to 24 months old (28 males). Several findings indicated FFG maturation throughout the first two years of life. First, right FFG responses to Face stimuli decreased as a function of age. Second, hemispheric specialization to the face stimuli developed somewhat slowly, with earlier right than left FFG peak activity most evident after 1 year of age. Right FFG activity to Face stimuli was of clinical interest, with an earlier right FFG response associated with better performance on tests assessing social and cognitive ability. Building on the above, clinical studies examining maturational change in FFG activity (e.g., lateralization and speed) in infants at-risk for childhood disorders associated with social deficits are of interest to identify atypical FFG maturation before a formal diagnosis is possible.