Asynchronous magnetic bead rotation microviscometer for rapid, sensitive, and label-free studies of bacterial growth and drug sensitivity.

The long turnaround time in antimicrobial susceptibility testing (AST) endangers patients and encourages the administration of wide spectrum antibiotics, thus resulting in alarming increases of multidrug resistant pathogens. A method for faster detection of bacterial proliferation presents one avenue toward addressing this global concern. We report on a label-free asynchronous magnetic bead rotation (AMBR) based viscometry method that rapidly detects bacterial growth and determines drug sensitivity by measuring changes in the suspension's viscosity. With this platform, we observed the growth of a uropathogenic Escherichia coli isolate, with an initial concentration of 50 cells per drop, within 20 min; in addition, we determined the gentamicin minimum inhibitory concentration (MIC) of the E. coli isolate within 100 min. We thus demonstrated a label-free, microviscometer platform that can measure bacterial growth and drug susceptibility more rapidly, with lower initial bacterial counts than existing commercial systems, and potentially with any microbial strains.

[1]  Roy Clarke,et al.  Magnetically uniform and tunable Janus particles , 2011 .

[2]  Fabrication of Nanoparticles and Microspheres with Uniform Magnetic Half-Shells , 2005 .

[3]  J. Kuntner,et al.  Characterizing the rheological behavior of oil-based liquids: microacoustic sensors versus rotational viscometers , 2005, IEEE Sensors Journal.

[4]  I. Sutherland Biofilm exopolysaccharides: a strong and sticky framework. , 2001, Microbiology.

[5]  Jeffrey N. Anker,et al.  Microrheology with modulated optical nanoprobes (MOONs) , 2005 .

[6]  Alastair D Hay,et al.  Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[7]  Shouzhuo Yao,et al.  The detection of Mycobacterium tuberculosis in sputum sample based on a wireless magnetoelastic-sensing device. , 2008, Talanta.

[8]  Brian N. Johnson,et al.  An integrated microfluidic device for influenza and other genetic analyses. , 2005, Lab on a chip.

[9]  J. Domínguez-Roldán,et al.  Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study , 2006, Critical care.

[10]  C A Grimes,et al.  A remote query magnetostrictive viscosity sensor. , 2000, Sensors and actuators. A, Physical.

[11]  P. Shankar,et al.  Experimental determination of the kinematic viscosity of glycerol-water mixtures , 1994, Proceedings of the Royal Society of London. Series A: Mathematical and Physical Sciences.

[12]  Andrey Sokolov,et al.  Reduction of viscosity in suspension of swimming bacteria. , 2009, Physical review letters.

[13]  Roy Clarke,et al.  Single bacterial cell detection with nonlinear rotational frequency shifts of driven magnetic microspheres , 2007 .

[14]  F. Greco,et al.  Effects of confinement on the motion of a single sphere in a sheared viscoelastic liquid , 2009 .

[15]  K. Sakai,et al.  Electromagnetically Spinning Sphere Viscometer , 2010 .

[16]  R. Kopelman,et al.  High frequency asynchronous magnetic bead rotation for improved biosensors. , 2010, Applied physics letters.

[17]  M. Burns,et al.  Asynchronous magnetic bead rotation (AMBR) biosensor in microfluidic droplets for rapid bacterial growth and susceptibility measurements. , 2011, Lab on a chip.

[18]  Zhenlu Cui Weakly sheared active suspensions: hydrodynamics, stability, and rheology. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[19]  R. Ismagilov,et al.  Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics. , 2008, Lab on a chip.

[20]  C. C. Ruiz,et al.  Fluid viscosity determination based on frequency domain time-resolved fluorescence anisotropy , 2010 .

[21]  Raoul Kopelman,et al.  Label-acquired magnetorotation as a signal transduction method for protein detection: aptamer-based detection of thrombin. , 2011, Analytical chemistry.

[22]  M. Ferraro,et al.  Antimicrobial susceptibility testing: general principles and contemporary practices. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  Roy Clarke,et al.  Compact sensor for measuring nonlinear rotational dynamics of driven magnetic microspheres with biomedical applications , 2009 .

[24]  Raoul Kopelman,et al.  Magnetically modulated optical nanoprobes , 2003 .

[25]  X. Wei,et al.  Cell concentration dependence of dynamic viscoelasticity of Escherichia coli culture suspensions , 1998 .

[26]  Vincent Gau,et al.  Antimicrobial susceptibility testing using high surface-to-volume ratio microchannels. , 2010, Analytical chemistry.

[27]  B. Jha,et al.  Bacterial exopolysaccharides – a perception , 2007, Journal of basic microbiology.

[28]  K G Ong,et al.  Monitoring of bacteria growth using a wireless, remote query resonant-circuit sensor: application to environmental sensing. , 2001, Biosensors & bioelectronics.

[29]  R. Kopelman,et al.  Physiochemical microparticle sensors based on nonlinear magnetic oscillations , 2007 .

[30]  B. Love,et al.  MMA bulk polymerization and its influence on in situ resin viscosity comparing several chemorheological models , 2011 .

[31]  Sriram Ramaswamy,et al.  Rheology of active-particle suspensions. , 2003, Physical review letters.

[32]  M. Burns,et al.  Monitoring the growth and drug susceptibility of individual bacteria using asynchronous magnetic bead rotation sensors. , 2011, Biosensors & bioelectronics.

[33]  M. Ferraro,et al.  Antimicrobial susceptibility testing: a review of general principles and contemporary practices. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[34]  J. Barenfanger,et al.  Clinical and Financial Benefits of Rapid Bacterial Identification and Antimicrobial Susceptibility Testing , 1999, Journal of Clinical Microbiology.

[35]  J. Andrews,et al.  Determination of minimum inhibitory concentrations. , 2001, The Journal of antimicrobial chemotherapy.

[36]  Salima Rafaï,et al.  Effective viscosity of microswimmer suspensions. , 2009, Physical review letters.

[37]  J. Martínez,et al.  A global view of antibiotic resistance. , 2009, FEMS microbiology reviews.

[38]  Raoul Kopelman,et al.  Label-acquired magnetorotation for biosensing: An asynchronous rotation assay. , 2011, Journal of magnetism and magnetic materials.

[39]  Raoul Kopelman,et al.  Sudden breakdown in linear response of a rotationally driven magnetic microparticle and application to physical and chemical microsensing. , 2006, The journal of physical chemistry. B.

[40]  P. Wong,et al.  A biosensor platform for rapid antimicrobial susceptibility testing directly from clinical samples. , 2011, The Journal of urology.

[41]  M. Shelley,et al.  Instabilities and pattern formation in active particle suspensions: kinetic theory and continuum simulations. , 2008, Physical review letters.