Detection of bacterial metabolites for the discrimination of bacteria utilizing gold nanoparticle chemiresistor sensors

Abstract The current methods for detecting and diagnosing bacterial infections have limitations that put lives at risk and threaten to burden healthcare systems with antibiotic resistant strains. Within the field of diagnostics, efforts continue to focus on developing new tools that are fast, easy to use and accessible to resource poor settings. Chemiresistor sensors are amongst new technologies being investigated to meet present needs for diagnosing diseases. Potential advantages of the technology include its amenability to point of care diagnostics, inexpensive components and rapid response times. Here, we present work on utilizing gold nanoparticle chemiresistors for the rapid detection and discrimination of bacteria in liquid samples. The detection principle is based on the distinct metabolic differences associated with species specific bacterial growth. For our proof of concept phase, the supernatant of defined bacterial liquid broth cultures were used. Principal component analysis on data from an array of gold nanoparticle chemiresistors was able to discriminate the culture supernatants of four bacterial species (Escherichia coli, Bacillus subtilis, Staphylococcus epidermidis and Enterobacter aerogenes). With basic unoptimized sensors, the detection limit for E. coli was indicated to be below 3.7 × 106 CFU/mL and detection was achieved within 6 h from low inoculation levels (102 CFU/mL). Results indicated for the first time that gold nanoparticle chemiresistors can successfully detect and discriminate bacteria indirectly from liquid samples. The outcome of this investigation is positive for the continued development of gold nanoparticle chemiresistors for a much needed point of care diagnostic tool for rapidly detecting bacteria.

[1]  J. P. Henderson,et al.  Development of an integrated metabolomic profiling approach for infectious diseases research. , 2011, The Analyst.

[2]  Keshun Yu,et al.  Comparison of long‐chain alcohols and other volatile compounds emitted from food‐borne and related Gram positive and Gram negative bacteria , 2002, Journal of basic microbiology.

[3]  B. Raguse,et al.  Gold Nanoparticle Chemiresistor Sensors in Aqueous Solution: Comparison of Hydrophobic and Hydrophilic Nanoparticle Films , 2009 .

[4]  R. W. Marshall,et al.  Detection and simultaneous identification of microorganisms from headspace samples using an electronic nose. , 1997 .

[5]  Dmitri Ivnitski,et al.  Biosensors for detection of pathogenic bacteria , 1999 .

[6]  Brian Taba,et al.  Colorimetric Sensor Array Allows Fast Detection and Simultaneous Identification of Sepsis-Causing Bacteria in Spiked Blood Culture , 2013, Journal of Clinical Microbiology.

[7]  David R Murdoch,et al.  Detection of volatile metabolites produced by bacterial growth in blood culture media by selected ion flow tube mass spectrometry (SIFT-MS). , 2006, Journal of microbiological methods.

[8]  Lee J. Hubble,et al.  Gold nanoparticle chemiresistors operating in biological fluids. , 2012, Lab on a chip.

[9]  J. Lindon,et al.  Systems biology: Metabonomics , 2008, Nature.

[10]  J. Perry,et al.  Identification of volatile organic compounds produced by bacteria using HS-SPME-GC-MS. , 2014, Journal of chromatographic science.

[11]  B. Raguse,et al.  Chemical Sensor Array That Can Differentiate Complex Hydrocarbon Mixtures Dissolved in Seawater , 2011 .

[12]  F. Caruso,et al.  Spontaneous phase transfer of nanoparticulate metals from organic to aqueous media. , 2001, Angewandte Chemie.

[13]  Michael L Wilson,et al.  Laboratory diagnosis of urinary tract infections in adult patients. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  H. Haick,et al.  Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors , 2010, British Journal of Cancer.

[15]  Burkhard Raguse,et al.  Gold nanoparticle chemiresistor sensors: direct sensing of organics in aqueous electrolyte solution. , 2007, Analytical chemistry.

[16]  Olivier Lazcka,et al.  Pathogen detection: a perspective of traditional methods and biosensors. , 2007, Biosensors & bioelectronics.

[17]  Yu W. Chu,et al.  Single step, rapid identification of pathogenic microorganisms in a culture bottle. , 2013, The Analyst.

[18]  Hossam Haick,et al.  Chemical sensors based on molecularly modified metallic nanoparticles , 2007 .

[19]  Jeroen S. Dickschat,et al.  Bacterial volatiles: the smell of small organisms. , 2007, Natural product reports.

[20]  J. W. Arnold,et al.  Use of digital aroma technology and SPME GC-MS to compare volatile compounds produced by bacteria isolated from processed poultry† , 1998 .

[21]  G. L. French,et al.  Diagnosis of Bacteriuria by Detection of Volatile Organic Compounds in Urine Using an Automated Headspace Analyzer with Multiple Conducting Polymer Sensors , 2001, Journal of Clinical Microbiology.

[22]  Jeffrey Wasserman,et al.  Global health diagnostics , 2006, Nature.

[23]  Mathias Brust,et al.  Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system , 1994 .

[24]  G. Schelling,et al.  Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[25]  David R Murdoch,et al.  The rapid evaluation of bacterial growth and antibiotic susceptibility in blood cultures by selected ion flow tube mass spectrometry. , 2006, Diagnostic microbiology and infectious disease.

[26]  J. Gardner,et al.  Biomedical Engineering Online Open Access Bacteria Classification Using Cyranose 320 Electronic Nose , 2022 .

[27]  T. Marrie,et al.  Streptococcus pneumoniae and Staphylococcus aureus pneumonia induce distinct metabolic responses. , 2009, Journal of proteome research.

[28]  Nicole Jaffrezic-Renault,et al.  Microconductometric immunosensor for label-free and sensitive detection of Gram-negative bacteria. , 2014, Biosensors & bioelectronics.

[29]  Anton Amann,et al.  Molecular analysis of volatile metabolites released specifically by staphylococcus aureus and pseudomonas aeruginosa , 2012, BMC Microbiology.

[30]  F. V. van Schooten,et al.  The versatile use of exhaled volatile organic compounds in human health and disease , 2012, Journal of breath research.

[31]  Keshun Yu,et al.  Production of the Long-Chain Alcohols Octanol, Decanol, and Dodecanol by Escherichia coli , 2005, Current Microbiology.

[32]  H. Haick,et al.  Diagnosing lung cancer in exhaled breath using gold nanoparticles. , 2009, Nature nanotechnology.

[33]  B. Raguse,et al.  Gold nanoparticle chemiresistor sensor array that differentiates between hydrocarbon fuels dissolved in artificial seawater. , 2010, Analytical chemistry.

[34]  S. Santra,et al.  Emerging nanotechnology-based strategies for the identification of microbial pathogenesis. , 2010, Advanced drug delivery reviews.

[35]  Tomas Mikoviny,et al.  On-Line Monitoring of Microbial Volatile Metabolites by Proton Transfer Reaction-Mass Spectrometry , 2008, Applied and Environmental Microbiology.

[36]  Jan Herrmann,et al.  Inkjet-printed gold nanoparticle chemiresistors: influence of film morphology and ionic strength on the detection of organics dissolved in aqueous solution. , 2009, Analytica chimica acta.

[37]  Arthur W. Snow,et al.  Colloidal Metal−Insulator−Metal Ensemble Chemiresistor Sensor , 1998 .

[38]  Peter J. Sterk,et al.  Volatile Metabolites of Pathogens: A Systematic Review , 2013, PLoS pathogens.

[39]  Lee J. Hubble,et al.  High-throughput fabrication and screening improves gold nanoparticle chemiresistor sensor performance. , 2015, ACS combinatorial science.

[40]  Jiangjiang Zhu,et al.  Fast Detection of Volatile Organic Compounds from Bacterial Cultures by Secondary Electrospray Ionization-Mass Spectrometry , 2010, Journal of Clinical Microbiology.

[41]  Harri Kiiveri,et al.  Quantifying mixtures of hydrocarbons dissolved in water with a partially selective sensor array using random forests analysis , 2014 .

[42]  L. Bret,et al.  Indole can act as an extracellular signal to regulate biofilm formation of Escherichia coli and other indole-producing bacteria. , 2003, Canadian journal of microbiology.