title: Rapid drug susceptibility test of Mycobacterium tuberculosis using microscopic time-lapse imaging in an agarose matrix.
abstract: Tuberculosis (TB) is a major global health problem, and multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are spreading throughout the world. However, conventional drug susceptibility test (DST) methods, which rely on the detection of the colony formation on a solid medium, require 1-2 months to the result. A rapid and accurate DST is necessary to identify patients with drug-resistant TB and treat them with appropriate drugs. Here, we used microscopic imaging of Mycobacterium tuberculosis (MTB) immobilized in an agarose matrix for a rapid DST. The agarose matrix, which was molded in a microfluidic chip, was inoculated with MTB, and TB drugs in liquid culture medium diffused throughout the agarose to reach the MTB immobilized in the agarose matrix. After the responses of MTB to drugs were tracked with an automated microscopic system, an image-processing program automatically determined the susceptibility and resistance of MTB to specific doses of TB drugs. The automatic DST system was able to assess the drug susceptibility of various drug-resistant clinical TB strains within 9 days with an accuracy comparable to that of conventional method. Our rapid DST method based on microscopic time-lapse imaging greatly reduces the time required for a DST and can be used to rapidly and accurately treat TB patients.
authors.affiliation: Department of Electrical Engineering and Computer Science, Seoul National University, San 56-1, Daehak-dong, Gwanak-gu, Seoul, 151-744, Republic of Korea.|QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.affiliation: QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jungheon
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Department of Biomedical Engineering, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, Republic of Korea.
authors.forename: Ki-Jung
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eun-Geun
authors.initials: EG
authors.lastname: Kim
authors.affiliation: QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyung Ock
authors.initials: KO
authors.lastname: Park
authors.affiliation: Korean Institute of Tuberculosis, Mansu-ri 482, Osong, Cheongju, Chungcheongbuk-do, 361-954, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Korean Institute of Tuberculosis, Mansu-ri 482, Osong, Cheongju, Chungcheongbuk-do, 361-954, Republic of Korea.
authors.forename: Haeun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Korean Institute of Tuberculosis, Mansu-ri 482, Osong, Cheongju, Chungcheongbuk-do, 361-954, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Jung
authors.affiliation: InSpace Co., Ltd., 96, Gajeongbuk-ro, Yuseong-gu, Daejeon, 305-343, Republic of Korea.
authors.forename: Taeyoung
authors.initials: T
authors.lastname: Kim
authors.affiliation: InSpace Co., Ltd., 96, Gajeongbuk-ro, Yuseong-gu, Daejeon, 305-343, Republic of Korea.
authors.forename: Myungjin
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, Republic of Korea.|Department of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hee Chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Korean Institute of Tuberculosis, Mansu-ri 482, Osong, Cheongju, Chungcheongbuk-do, 361-954, Republic of Korea. viweon@naver.com.
authors.forename: Sungweon
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea. jygpaul@quantamatrix.com.
authors.forename: Yong-Gyun
authors.initials: YG
authors.lastname: Jung
authors.affiliation: Department of Electrical Engineering and Computer Science, Seoul National University, San 56-1, Daehak-dong, Gwanak-gu, Seoul, 151-744, Republic of Korea. skwon@snu.ac.kr.|QuantaMatrix Inc., 104-213, Seoul National University, Seoul, Republic of Korea. skwon@snu.ac.kr.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kwon
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D057205:Automation, Laboratory / Q000379:methods; D005782:Gels; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000295:instrumentation / Q000379:methods*; D044085:Microfluidics / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012685:Sepharose; D013997:Time Factors; D059008:Time-Lapse Imaging / Q000379:methods*
chemical_list: D000995:Antitubercular Agents; D005782:Gels; D012685:Sepharose
keywords: Automation; Drug susceptibility test; Microscopic imaging; Tuberculosis