Multiplexed identification, quantification and genotyping of infectious agents using a semiconductor biochip NATURE BIOTECHNOLOGY Hassibi, A., Manickam, A., Singh, R., Bolouki, S., Sinha, R., Jirage, K. B., McDermott, M. W., Hassibi, B., Vikalo, H., Mazarei, G., Pei, L., Bousse, L., Miller, M., Heshami, M., Savage, M. P., Taylor, M. T., Gamini, N., Wood, N., Mantina, P., Grogan, P., Kuimelis, P., Savalia, P., Conradson, S., Li, Y., Meyer, R. B., Ku, E., Ebert, J., Pinsky, B. A., Dolganov, G., Van, T., Johnson, K. A., Naraghi-Arani, P., Kuimelis, R. G., Schoolnik, G. 2018; 36 (8): 738–45


The emergence of pathogens resistant to existing antimicrobial drugs is a growing worldwide health crisis that threatens a return to the pre-antibiotic era. To decrease the overuse of antibiotics, molecular diagnostics systems are needed that can rapidly identify pathogens in a clinical sample and determine the presence of mutations that confer drug resistance at the point of care. We developed a fully integrated, miniaturized semiconductor biochip and closed-tube detection chemistry that performs multiplex nucleic acid amplification and sequence analysis. The approach had a high dynamic range of quantification of microbial load and was able to perform comprehensive mutation analysis on up to 1,000 sequences or strands simultaneously in <2 h. We detected and quantified multiple DNA and RNA respiratory viruses in clinical samples with complete concordance to a commercially available test. We also identified 54 drug-resistance-associated mutations that were present in six genes of Mycobacterium tuberculosis, all of which were confirmed by next-generation sequencing.

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