Adaptable microfluidic system for single-cell pathogen classification and antimicrobial susceptibility testing

被引:104
作者
Li, Hui [1 ]
Torab, Peter [2 ]
Mach, Kathleen E. [3 ]
Surrette, Christine [4 ]
England, Matthew R. [5 ]
Craft, David W. [5 ]
Thomas, Neal J. [6 ,7 ]
Liao, Joseph C. [3 ]
Puleo, Chris [4 ]
Wong, Pak Kin [1 ,2 ,8 ]
机构
[1] Penn State Univ, Dept Biomed Engn, University Pk, PA 16802 USA
[2] Penn State Univ, Dept Mech Engn, University Pk, PA 16802 USA
[3] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA
[4] GE Global Res, Elect Org, Niskayuna, NY 12309 USA
[5] Penn State Milton S Hershey Med Ctr, Pathol & Lab Med, Hershey, PA 17033 USA
[6] Penn State Univ, Dept Pediat, Coll Med, Hershey, PA 17033 USA
[7] Penn State Univ, Dept Publ Hlth Sci, Coll Med, Hershey, PA 17033 USA
[8] Penn State Univ, Dept Surg, Coll Med, Hershey, PA 17033 USA
关键词
infection; diagnostics; antimicrobial susceptibility testing; single-cell analysis; microfluidics; ANTIBIOTIC SUSCEPTIBILITY; BACTERIAL CULTURE; IDENTIFICATION; DIAGNOSIS; TRACKING; PLATFORM; GROWTH; CANINE;
D O I
10.1073/pnas.1819569116
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Infectious diseases caused by bacterial pathogens remain one of the most common causes of morbidity and mortality worldwide. Rapid microbiological analysis is required for prompt treatment of bacterial infections and to facilitate antibiotic stewardship. This study reports an adaptable microfluidic system for rapid pathogen classification and antimicrobial susceptibility testing (AST) at the single-cell level. By incorporating tunable microfluidic valves along with real-time optical detection, bacteria can be trapped and classified according to their physical shape and size for pathogen classification. By monitoring their growth in the presence of antibiotics at the single-cell level, antimicrobial susceptibility of the bacteria can be determined in as little as 30 minutes compared with days required for standard procedures. The microfluidic system is able to detect bacterial pathogens in urine, blood cultures, and whole blood and can analyze polymicrobial samples. We pilot a study of 25 clinical urine samples to demonstrate the clinical applicability of the microfluidic system. The platform demonstrated a sensitivity of 100% and specificity of 83.33% for pathogen classification and achieved 100% concordance for AST.
引用
收藏
页码:10270 / 10279
页数:10
相关论文
共 47 条
[1]  
[Anonymous], 2015, Global Antimicrobial Resistance and Use Surveillance System (GLASS)
[2]  
[Anonymous], 2015, M100S25 CLSI
[3]  
[Anonymous], 2012, METHODS DILUTION ANT, VNinth
[4]   Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays [J].
Avesar, Jonathan ;
Rosenfeld, Dekel ;
Truman-Rosentsvit, Marianna ;
Ben-Arye, Tom ;
Geffen, Yuval ;
Bercovici, Moran ;
Levenberg, Shulamit .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (29) :E5787-E5795
[5]   Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging [J].
Baltekin, Ozden ;
Boucharin, Alexis ;
Tano, Eva ;
Andersson, Dan I. ;
Elf, Johan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (34) :9170-9175
[6]   Review of Rapid Diagnostic Tests Used by Antimicrobial Stewardship Programs [J].
Bauer, Karri A. ;
Perez, Katherine K. ;
Forrest, Graeme N. ;
Goff, Debra A. .
CLINICAL INFECTIOUS DISEASES, 2014, 59 :S134-S145
[7]   Rapid electrochemical phenotypic profiling of antibiotic-resistant bacteria [J].
Besant, Justin D. ;
Sargent, Edward H. ;
Kelley, Shana O. .
LAB ON A CHIP, 2015, 15 (13) :2799-2807
[8]   Molecular mechanisms of antibiotic resistance [J].
Blair, Jessica M. A. ;
Webber, Mark A. ;
Baylay, Alison J. ;
Ogbolu, David O. ;
Piddock, Laura J. V. .
NATURE REVIEWS MICROBIOLOGY, 2015, 13 (01) :42-51
[9]   Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics [J].
Boedicker, James Q. ;
Li, Liang ;
Kline, Timothy R. ;
Ismagilov, Rustem F. .
LAB ON A CHIP, 2008, 8 (08) :1265-1272
[10]   Antianaerobic Antimicrobials: Spectrum and Susceptibility Testing [J].
Brook, Itzhak ;
Wexler, Hannah M. ;
Goldstein, Ellie J. C. .
CLINICAL MICROBIOLOGY REVIEWS, 2013, 26 (03) :526-546