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Title: Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs

Abstract

Time-consuming, expensive and low sensitivity diagnostic methods used for monitoring bacterial infections lead to unnecessary or delays in prescription of the right antibiotic treatment. Determining an optimal clinical treatment requires rapid detection and identification of pathogenic bacteria and their sensitivity to specific antimicrobials. However, diagnostic devices that meet all of these criteria have proven elusive thus far. Graphene field effect transistors (G-FET) are a promising solution, since they are highly sensitive to chemical/biological modification, can have fast detection times and can be placed on different substrates. Here, by integrating specific peptide probes over G-FETs, we present a proof-of-concept study for species and strain specific label-free detection of clinical strains of pathogenic bacteria with high specificity and sensitivity. We found that pyrene-conjugated peptides immobilized on G-FETs were capable of detecting pathogenic Staphylococcus aureus at the single-cell level and discriminate against other gram-positive and gram-negative bacterial pathogens. A similar device was able to discriminate between antibiotic resistant and sensitive strains of Acinetobacter baumannii , suggesting that these devices can also be used for detecting antibiotic resistive pathogens. Furthermore, a new means of enhancing attachment, electric-field assisted binding, reduced the detection limit to 104 cells/ml and the detection time to below 5 minutes.more » Here, the combination of single step attachment, inexpensive production, rapid, selective and sensitive detection suggest G-FETs plus pyrene-conjugated peptides are a new platform for solving major challenges faced in point of care diagnostics to fight infectious diseases and antimicrobial resistance.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [1];  [1];  [1]
  1. Boston College, Chestnut Hill, MA (United States)
  2. Boston Univ., MA (United States)
Publication Date:
Research Org.:
Boston College, Chestnut Hill, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division; National Institutes of Health (NIH); National Science Foundation (NSF); USDOE
OSTI Identifier:
1780972
Alternate Identifier(s):
OSTI ID: 1603705
Grant/Contract Number:  
SC0018675; R01-AI110724; U01-AI124302; R01-GM102735; R01-GM124231; DMR-1709987; BIO-1460628
Resource Type:
Accepted Manuscript
Journal Name:
Biosensors and Bioelectronics
Additional Journal Information:
Journal Volume: 156; Journal ID: ISSN 0956-5663
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; Biosensors; G-FET; Peptide probes; Dielectrophoresis; Antibiotic resistance bacteria; Electrical detection

Citation Formats

Kumar, Narendra, Wang, Wenjian, Ortiz-Marquez, Juan C., Catalano, Matthew, Gray, Mason, Biglari, Nadia, Hikari, Kitadai, Ling, Xi, Gao, Jianmin, van Opijnen, Tim, and Burch, Kenneth S. Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs. United States: N. p., 2020. Web. doi:10.1016/j.bios.2020.112123.
Kumar, Narendra, Wang, Wenjian, Ortiz-Marquez, Juan C., Catalano, Matthew, Gray, Mason, Biglari, Nadia, Hikari, Kitadai, Ling, Xi, Gao, Jianmin, van Opijnen, Tim, & Burch, Kenneth S. Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs. United States. https://doi.org/10.1016/j.bios.2020.112123
Kumar, Narendra, Wang, Wenjian, Ortiz-Marquez, Juan C., Catalano, Matthew, Gray, Mason, Biglari, Nadia, Hikari, Kitadai, Ling, Xi, Gao, Jianmin, van Opijnen, Tim, and Burch, Kenneth S. Thu . "Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs". United States. https://doi.org/10.1016/j.bios.2020.112123. https://www.osti.gov/servlets/purl/1780972.
@article{osti_1780972,
title = {Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs},
author = {Kumar, Narendra and Wang, Wenjian and Ortiz-Marquez, Juan C. and Catalano, Matthew and Gray, Mason and Biglari, Nadia and Hikari, Kitadai and Ling, Xi and Gao, Jianmin and van Opijnen, Tim and Burch, Kenneth S.},
abstractNote = {Time-consuming, expensive and low sensitivity diagnostic methods used for monitoring bacterial infections lead to unnecessary or delays in prescription of the right antibiotic treatment. Determining an optimal clinical treatment requires rapid detection and identification of pathogenic bacteria and their sensitivity to specific antimicrobials. However, diagnostic devices that meet all of these criteria have proven elusive thus far. Graphene field effect transistors (G-FET) are a promising solution, since they are highly sensitive to chemical/biological modification, can have fast detection times and can be placed on different substrates. Here, by integrating specific peptide probes over G-FETs, we present a proof-of-concept study for species and strain specific label-free detection of clinical strains of pathogenic bacteria with high specificity and sensitivity. We found that pyrene-conjugated peptides immobilized on G-FETs were capable of detecting pathogenic Staphylococcus aureus at the single-cell level and discriminate against other gram-positive and gram-negative bacterial pathogens. A similar device was able to discriminate between antibiotic resistant and sensitive strains of Acinetobacter baumannii , suggesting that these devices can also be used for detecting antibiotic resistive pathogens. Furthermore, a new means of enhancing attachment, electric-field assisted binding, reduced the detection limit to 104 cells/ml and the detection time to below 5 minutes. Here, the combination of single step attachment, inexpensive production, rapid, selective and sensitive detection suggest G-FETs plus pyrene-conjugated peptides are a new platform for solving major challenges faced in point of care diagnostics to fight infectious diseases and antimicrobial resistance.},
doi = {10.1016/j.bios.2020.112123},
journal = {Biosensors and Bioelectronics},
number = ,
volume = 156,
place = {United States},
year = {Thu Feb 27 00:00:00 EST 2020},
month = {Thu Feb 27 00:00:00 EST 2020}
}

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Works referenced in this record:

Graphene transistors for interfacing with cells: towards a deeper understanding of liquid gating and sensitivity
journal, July 2017


Biosensors for rapid and sensitive detection of Staphylococcus aureus in food
journal, May 2018


Diagnosis of Urinary Tract Infections in Children
journal, April 2016

  • Doern, Christopher D.; Richardson, Susan E.
  • Journal of Clinical Microbiology, Vol. 54, Issue 9
  • DOI: 10.1128/JCM.00189-16

Antimicrobial peptides of multicellular organisms
journal, January 2002


Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics
journal, April 2018

  • McCarthy, Kelly A.; Kelly, Michael A.; Li, Kaicheng
  • Journal of the American Chemical Society, Vol. 140, Issue 19
  • DOI: 10.1021/jacs.8b02461

INFECTIOUS DISEASE:PCR Detection of Bacteria in Seven Minutes
journal, April 1999


Biosensors for Whole-Cell Bacterial Detection
journal, June 2014

  • Ahmed, A.; Rushworth, J. V.; Hirst, N. A.
  • Clinical Microbiology Reviews, Vol. 27, Issue 3
  • DOI: 10.1128/CMR.00120-13

Identification of a strong contamination source for graphene in vacuum systems
journal, September 2013


The United Nations and the Urgent Need for Coordinated Global Action in the Fight Against Antimicrobial Resistance
journal, September 2016

  • Boucher, Helen W.; Bakken, Johan S.; Murray, Barbara E.
  • Annals of Internal Medicine, Vol. 165, Issue 11
  • DOI: 10.7326/M16-2079

An aptameric graphene nanosensor for label-free detection of small-molecule biomarkers
journal, September 2015


Sensing at the Surface of Graphene Field-Effect Transistors
journal, November 2016

  • Fu, Wangyang; Jiang, Lin; van Geest, Erik P.
  • Advanced Materials, Vol. 29, Issue 6
  • DOI: 10.1002/adma.201603610

Graphene field-effect transistors: the road to bioelectronics
journal, September 2018

  • Donnelly, Matthew; Mao, Dacheng; Park, Junsu
  • Journal of Physics D: Applied Physics, Vol. 51, Issue 49
  • DOI: 10.1088/1361-6463/aadcca

Graphene-based biosensors for detection of bacteria and their metabolic activities
journal, January 2011

  • Huang, Yinxi; Dong, Xiaochen; Liu, Yuxin
  • Journal of Materials Chemistry, Vol. 21, Issue 33, 12358-12362
  • DOI: 10.1039/c1jm11436k

Alterations in ambipolar characteristic of graphene due to adsorption of Escherichia coli bacteria
journal, February 2018

  • Mulyana, Yana; Uenuma, Mutsunori; Okamoto, Naofumi
  • Journal of Physics D: Applied Physics, Vol. 51, Issue 11
  • DOI: 10.1088/1361-6463/aaac6e

Graphene-based wireless bacteria detection on tooth enamel
journal, January 2012

  • Mannoor, Manu S.; Tao, Hu; Clayton, Jefferson D.
  • Nature Communications, Vol. 3, Issue 1
  • DOI: 10.1038/ncomms1767

Rapid Bacterial Detection via an All-Electronic CMOS Biosensor
journal, September 2016


Electrical detection of pathogenic bacteria via immobilized antimicrobial peptides
journal, October 2010

  • Mannoor, M. S.; Zhang, S.; Link, A. J.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 45
  • DOI: 10.1073/pnas.1008768107

Methods for the detection and identification of pathogenic bacteria: past, present, and future
journal, January 2017

  • Váradi, Linda; Luo, Jia Lin; Hibbs, David E.
  • Chemical Society Reviews, Vol. 46, Issue 16
  • DOI: 10.1039/C6CS00693K

Rapid Cytometric Antibiotic Susceptibility Testing Utilizing Adaptive Multidimensional Statistical Metrics
journal, January 2015

  • Huang, Tzu-Hsueh; Ning, Xinghai; Wang, Xiaojian
  • Analytical Chemistry, Vol. 87, Issue 3
  • DOI: 10.1021/ac504241x

Biomimetic Chemosensor: Designing Peptide Recognition Elements for Surface Functionalization of Carbon Nanotube Field Effect Transistors
journal, December 2009

  • Kuang, Zhifeng; Kim, Sang N.; Crookes-Goodson, Wendy J.
  • ACS Nano, Vol. 4, Issue 1
  • DOI: 10.1021/nn901365g

Functionalization of Graphene: Covalent and Non-Covalent Approaches, Derivatives and Applications
journal, September 2012

  • Georgakilas, Vasilios; Otyepka, Michal; Bourlinos, Athanasios B.
  • Chemical Reviews, Vol. 112, Issue 11
  • DOI: 10.1021/cr3000412

Current and emerging techniques for antibiotic susceptibility tests
journal, January 2017


A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii
journal, September 2016

  • Boll, Joseph M.; Crofts, Alexander A.; Peters, Katharina
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 41
  • DOI: 10.1073/pnas.1611594113

Discovering and improving novel peptide therapeutics
journal, October 2008


Scalable Production of High-Sensitivity, Label-Free DNA Biosensors Based on Back-Gated Graphene Field Effect Transistors
journal, September 2016


Inexpensive and fast pathogenic bacteria screening using field-effect transistors
journal, November 2016


Membrane potential and gentamicin uptake in Staphylococcus aureus.
journal, November 1982

  • Mates, S. M.; Eisenberg, E. S.; Mandel, L. J.
  • Proceedings of the National Academy of Sciences, Vol. 79, Issue 21
  • DOI: 10.1073/pnas.79.21.6693

Effect of zeta potential value on bacterial behavior during electrophoretic separation
journal, May 2010

  • Kłodzińska, Ewa; Szumski, Michał; Dziubakiewicz, Ewelina
  • ELECTROPHORESIS, Vol. 31, Issue 9
  • DOI: 10.1002/elps.200900559

Cell shape dynamics during the staphylococcal cell cycle
journal, August 2015

  • Monteiro, João M.; Fernandes, Pedro B.; Vaz, Filipa
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms9055

Graphene Field-Effect Transistors for the Sensitive and Selective Detection of Escherichia coli Using Pyrene-Tagged DNA Aptamer
journal, August 2017

  • Wu, Guangfu; Dai, Ziwen; Tang, Xin
  • Advanced Healthcare Materials, Vol. 6, Issue 19
  • DOI: 10.1002/adhm.201700736

Label-free detection of DNA hybridization using transistors based on CVD grown graphene
journal, March 2013


Label-free detection of Staphylococcus aureus bacteria using long-period fiber gratings with functional polyelectrolyte coatings
journal, May 2019


Carbapenem-Nonsusceptible Acinetobacter baumannii , 8 US Metropolitan Areas, 2012–2015
journal, April 2018

  • Bulens, Sandra N.; Yi, Sarah H.; Walters, Maroya S.
  • Emerging Infectious Diseases, Vol. 24, Issue 4
  • DOI: 10.3201/eid2404.171461

Rapid point of care diagnostic tests for viral and bacterial respiratory tract infections—needs, advances, and future prospects
journal, November 2014


Impedimetric Detection of Pathogenic Gram-Positive Bacteria Using an Antimicrobial Peptide from Class IIa Bacteriocins
journal, January 2014

  • Etayash, Hashem; Jiang, Keren; Thundat, Thomas
  • Analytical Chemistry, Vol. 86, Issue 3
  • DOI: 10.1021/ac4034938

Raman spectroscopy of graphene-based materials and its applications in related devices
journal, January 2018

  • Wu, Jiang-Bin; Lin, Miao-Ling; Cong, Xin
  • Chemical Society Reviews, Vol. 47, Issue 5
  • DOI: 10.1039/C6CS00915H

Biosensing near the neutrality point of graphene
journal, October 2017

  • Fu, Wangyang; Feng, Lingyan; Panaitov, Gregory
  • Science Advances, Vol. 3, Issue 10
  • DOI: 10.1126/sciadv.1701247

Minireview: Trends in Optical-Based Biosensors for Point-Of-Care Bacterial Pathogen Detection for Food Safety and Clinical Diagnostics
journal, May 2018


Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor
journal, March 2017

  • Xu, Shicai; Zhan, Jian; Man, Baoyuan
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms14902

Empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures
journal, September 2015

  • Scholte, J. B. J.; Duong, H. L.; Linssen, C.
  • European Journal of Clinical Microbiology & Infectious Diseases, Vol. 34, Issue 11
  • DOI: 10.1007/s10096-015-2482-y

Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection
journal, June 2015

  • López-Góngora, Sheila; Puig, Ignasi; Calvet, Xavier
  • Journal of Antimicrobial Chemotherapy, Vol. 70, Issue 9
  • DOI: 10.1093/jac/dkv155

Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults
journal, March 2005

  • Nicolle, Lindsay E.; Bradley, Suzanne; Colgan, Richard
  • Clinical Infectious Diseases, Vol. 40, Issue 5
  • DOI: 10.1086/427507

Developmental roadmap for antimicrobial susceptibility testing systems
journal, October 2018

  • van Belkum, Alex; Bachmann, Till T.; Lüdke, Gerd
  • Nature Reviews Microbiology, Vol. 17, Issue 1
  • DOI: 10.1038/s41579-018-0098-9

Ligands for label-free detection of whole bacteria on biosensors: A review
journal, May 2016


Rapid detection of single E. coli bacteria using a graphene-based field-effect transistor device
journal, July 2018


Current Concepts in Laboratory Testing to Guide Antimicrobial Therapy
journal, March 2012


Excess Costs and Utilization Associated with Methicillin Resistance for Patients with Staphylococcus aureus Infection
journal, April 2010

  • Filice, Gregory A.; Nyman, John A.; Lexau, Catherine
  • Infection Control & Hospital Epidemiology, Vol. 31, Issue 4
  • DOI: 10.1086/651094

Effect of zeta potential value on bacterial behavior during electrophoretic separation
journal, May 2010

  • Kłodzińska, Ewa; Szumski, Michał; Dziubakiewicz, Ewelina
  • ELECTROPHORESIS, Vol. 31, Issue 9
  • DOI: 10.1002/elps.200900559

Empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures
journal, September 2015

  • Scholte, J. B. J.; Duong, H. L.; Linssen, C.
  • European Journal of Clinical Microbiology & Infectious Diseases, Vol. 34, Issue 11
  • DOI: 10.1007/s10096-015-2482-y

Ligands for label-free detection of whole bacteria on biosensors: A review
journal, May 2016


Scalable Production of High-Sensitivity, Label-Free DNA Biosensors Based on Back-Gated Graphene Field Effect Transistors
journal, September 2016


A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii
journal, September 2016

  • Boll, Joseph M.; Crofts, Alexander A.; Peters, Katharina
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 41
  • DOI: 10.1073/pnas.1611594113

Excess Costs and Utilization Associated with Methicillin Resistance for Patients with Staphylococcus aureus Infection
journal, April 2010

  • Filice, Gregory A.; Nyman, John A.; Lexau, Catherine
  • Infection Control & Hospital Epidemiology, Vol. 31, Issue 4
  • DOI: 10.1086/651094