The Detection of Helicobacter hepaticus Using Whispering-Gallery Mode Microcavity Optical Sensors

Current bacterial detection techniques are relatively slow, require bulky instrumentation, and usually require some form of specialized training. The gold standard for bacterial detection is culture testing, which can take several days to receive a viable result. Therefore, simpler detection techniques that are both fast and sensitive could greatly improve bacterial detection and identification. Here, we present a new method for the detection of the bacteria Helicobacter hepaticus using whispering-gallery mode (WGM) optical microcavity-based sensors. Due to minimal reflection losses and low material adsorption, WGM-based sensors have ultra-high quality factors, resulting in high-sensitivity sensor devices. In this study, we have shown that bacteria can be non-specifically detected using WGM optical microcavity-based sensors. The minimum detection for the device was 1 × 104 cells/mL, and the minimum time of detection was found to be 750 s. Given that a cell density as low as 1 × 103 cells/mL for Helicobacter hepaticus can cause infection, the limit of detection shown here would be useful for most levels where Helicobacter hepaticus is biologically relevant. This study suggests a new approach for H. hepaticus detection using label-free optical sensors that is faster than, and potentially as sensitive as, standard techniques.

[1]  Jörg P Kutter,et al.  Optical detection in microfluidic systems , 2009, Electrophoresis.

[2]  G. Nyakatura,et al.  The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Lan Yang,et al.  On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh- Q microresonator , 2010 .

[4]  Heather K Hunt,et al.  Label-free biological and chemical sensors. , 2010, Nanoscale.

[5]  Lan Yang,et al.  Review Label-free detection with high-Q microcavities: a review of biosensing mechanisms for integrated devices , 2012 .

[6]  S. Arnold,et al.  Single virus detection from the reactive shift of a whispering-gallery mode , 2008, Proceedings of the National Academy of Sciences.

[7]  Muzammil Iqbal,et al.  Characterization of the evanescent field profile and bound mass sensitivity of a label-free silicon photonic microring resonator biosensing platform. , 2010, Biosensors & bioelectronics.

[8]  J. Jordan,et al.  Molecular Detection of Culture-Confirmed Bacterial Bloodstream Infections with Limited Enrichment Time , 2013, Journal of Clinical Microbiology.

[9]  M. Boissinot,et al.  Toward Automatic Label-Free Whispering Gallery Modes Biodetection with a Quantum Dot-Coated Microsphere Population , 2010, Nanoscale research letters.

[10]  K. Chayama,et al.  Detection of Helicobacter hepaticus in Human Bile Samples of Patients with Biliary Disease , 2009, Helicobacter.

[11]  R L Lundblad,et al.  Colorimetric protein assay techniques , 1999, Biotechnology and applied biochemistry.

[12]  Mark Borodovsky,et al.  The complete genome sequence of the gastric pathogen Helicobacter pylori , 1997, Nature.

[13]  Xudong Fan,et al.  Analysis of single nanoparticle detection by using 3-dimensionally confined optofluidic ring resonators , 2010, Asia Communications and Photonics Conference and Exhibition.

[14]  N. Pourmand,et al.  Label-Free Impedance Biosensors: Opportunities and Challenges. , 2007, Electroanalysis.

[15]  K. Vahala Optical microcavities , 2003, Nature.

[16]  Yuze Sun,et al.  Sensitive optical biosensors for unlabeled targets: a review. , 2008, Analytica chimica acta.

[17]  Khalil Arshak,et al.  An overview of foodborne pathogen detection: in the perspective of biosensors. , 2010, Biotechnology advances.

[18]  P. Kenny,et al.  Comment on: Rich and Myszka, Grading the commercial optical biosensor literature—Class of 2008: ‘The Mighty Binders’. J. Mol. Recognit. 2010, 23, 1–64. , 2010, Journal of molecular recognition : JMR.

[19]  J. Ward,et al.  Inflammatory large bowel disease in immunodeficient mice naturally infected with Helicobacter hepaticus. , 1996, Laboratory animal science.

[20]  Frank Vollmer,et al.  High-Q microsphere biosensor - analysis for adsorption of rodlike bacteria. , 2007, Optics express.

[21]  R. Norwood,et al.  Label-free, single-object sensing with a microring resonator: FDTD simulation. , 2013, Optics express.

[22]  Lei Wang,et al.  Optical aptasensors for quantitative detection of small biomolecules: a review. , 2014, Biosensors & bioelectronics.

[23]  Rajan P Kulkarni,et al.  Label-Free, Single-Molecule Detection with Optical Microcavities , 2007, Science.

[24]  Kerry J. Vahala,et al.  Fabrication and coupling to planar high-Q silica disk microcavities , 2003 .

[25]  Achim Peters,et al.  An alignment-free fiber-coupled microsphere resonator for gas sensing applications , 2010 .

[26]  Rebecca L. Rich,et al.  Grading the commercial optical biosensor literature—Class of 2008: ‘The Mighty Binders’ , 2009, Journal of molecular recognition : JMR.

[27]  Audrey Sassolas,et al.  Optical detection systems using immobilized aptamers. , 2011, Biosensors & bioelectronics.

[28]  Ismail Hakki Boyaci,et al.  Rapid and label‐free bacteria detection by surface plasmon resonance (SPR) biosensors , 2009, Biotechnology journal.

[29]  Joachim Knittel,et al.  Detection of nanoparticles with a frequency locked whispering gallery mode microresonator , 2013, 1303.1174.

[30]  Michael Hochberg,et al.  Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma. , 2013, Biosensors & bioelectronics.

[31]  M. Cooper Label-free screening of bio-molecular interactions , 2003, Analytical and bioanalytical chemistry.

[32]  J. Solnick,et al.  Inflammation, Immunity, and Vaccine Development for Helicobacter pylori , 2011, Helicobacter.

[33]  Heather K Hunt,et al.  Attaching biological probes to silica optical biosensors using silane coupling agents. , 2012, Journal of visualized experiments : JoVE.

[34]  Alexandre François,et al.  Optical Sensors Based on Whispering Gallery Modes in Fluorescent Microbeads: Response to Specific Interactions , 2010, Sensors.

[35]  Alessandro Chiasera,et al.  Spherical whispering‐gallery‐mode microresonators , 2010 .

[36]  Ye Fang The development of label-free cellular assays for drug discovery , 2011, Expert opinion on drug discovery.

[37]  N. Dilbaghi,et al.  Biosensors as innovative tools for the detection of food borne pathogens. , 2011, Biosensors & bioelectronics.

[38]  J. Chow,et al.  Ultrasensitive real-time measurement of dissipation and dispersion in a whispering-gallery mode microresonator. , 2013, Optics letters.

[39]  M. Gorodetsky,et al.  Ultimate Q of optical microsphere resonators. , 1996, Optics letters.

[40]  Q. Cheng,et al.  New trends in instrumental design for surface plasmon resonance-based biosensors. , 2011, Biosensors & bioelectronics.

[41]  Christopher Pöhlmann,et al.  Rapid, specific and sensitive electrochemical detection of foodborne bacteria. , 2009, Biosensors & bioelectronics.

[42]  Heather K Hunt,et al.  Tailoring the protein adsorption properties of whispering gallery mode optical biosensors. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[43]  I. Badr,et al.  Highly selective optical fluoride ion sensor with submicromolar detection limit based on aluminum(III) octaethylporphyrin in thin polymeric film. , 2005, Journal of the American Chemical Society.

[44]  L. Novotny,et al.  Optical Detection of Single Nanoparticles and Viruses , 2006, IEEE Journal of Selected Topics in Quantum Electronics.

[45]  J. Taneera,et al.  Identification of Helicobacter pylori and OtherHelicobacter Species by PCR, Hybridization, and Partial DNA Sequencing in Human Liver Samples from Patients with Primary Sclerosing Cholangitis or Primary Biliary Cirrhosis , 2000, Journal of Clinical Microbiology.

[46]  E. Diamadopoulos,et al.  Detection and fate of antibiotic resistant bacteria in wastewater treatment plants: a review. , 2013, Ecotoxicology and environmental safety.

[47]  Guo-Qiang Lo,et al.  Label-free biosensor based on an electrical tracing-assisted silicon microring resonator with a low-cost broadband source. , 2013, Biosensors & bioelectronics.

[48]  Franco Cosi,et al.  Optical Microspherical Resonators for Biomedical Sensing , 2011, Sensors.

[49]  Matthew R Foreman,et al.  Whispering gallery mode sensors. , 2015, Advances in optics and photonics.

[50]  T. J. Kippenberg,et al.  Ultra-high-Q toroid microcavity on a chip , 2003, Nature.