Multiplexed identification, quantification and genotyping of infectious agents using a semiconductor biochip

Nature Biotechnology
Arjang HassibiGary Schoolnik

Abstract

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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Citations

Oct 23, 2019·The Journal of Applied Laboratory Medicine·Alexander L Greninger, Samia N Naccache
Apr 30, 2020·Nature·Cheri M AckermanPardis C Sabeti
Apr 9, 2020·BMC Infectious Diseases·Jie ChenZhan-Wei Ruan
Jun 27, 2019·Nature Biotechnology·Themoula CharalampousJustin O'Grady
Aug 8, 2020·Frontiers in Cellular and Infection Microbiology·Antti VasalaOlli H Laitinen
Nov 6, 2020·Nucleic Acids Research·Ignacio Moya-RamírezKaren Polizzi
Jul 18, 2020·Trends in Microbiology·Huaqi TangAlireza Mashaghi
Jul 3, 2021·Micromachines·Peng SunDongping Wu
Nov 6, 2021·Frontiers in Cellular and Infection Microbiology·Shengrui MuBin Cao

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