Research review paper Colorimetric biosensing of pathogens using gold nanoparticles Mohit S. Verma a,b , Jacob L. Rogowski a,b , Lyndon Jones a,c , Frank X. Gu a,b, a Department of Chemical Engineering, University of Waterloo, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada b Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada c Center for Contact Lens Research, University of Waterloo, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada abstract article info Article history: Received 25 September 2014 Received in revised form 8 February 2015 Accepted 2 March 2015 Available online 17 March 2015 Keywords: Bacteria Virus Fungus Point-of-care DNA RNA Protein Small molecule PCR Color Rapid detection of pathogens is crucial to minimize adverse health impacts of nosocomial, foodborne, and water- borne diseases. Gold nanoparticles are extremely successful at detecting pathogens due to their ability to provide a simple and rapid color change when their environment is altered. Here, we review general strategies of implementing gold nanoparticles in colorimetric biosensors. First, we highlight how gold nanoparticles have improved conventional genomic analysis methods by lowering detection limits while reducing assay times. Then, we focus on emerging point-of-care technologies that aim at pathogen detection using simpler assays. These advances will facilitate the implementation of gold nanoparticle-based biosensors in diverse environments throughout the world and help prevent the spread of infectious diseases. © 2015 Elsevier Inc. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667 2. Conventional methods for pathogen detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667 3. Principles of gold nanoparticle sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668 4. Gold nanoparticles for detecting nucleic acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669 4.1. Gold nanoparticles for amplied nucleic acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669 4.1.1. Non-functionalized gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669 4.1.2. Functionalized gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669 4.2. Gold nanoparticles for unamplied nucleic acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 672 4.2.1. Non-functionalized gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 672 4.2.2. Functionalized gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 672 5. Emerging biosensors for detecting non-nucleic acid analytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673 5.1. Non-functionalized gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673 5.2. Gold nanoparticles functionalized with proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 674 5.3. Gold nanoparticles functionalized with small molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675 6. Comparison of gold nanoparticles to conventional methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 6.1. Analysis time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 6.2. Limit of detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 6.3. Specicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678 6.4. Technical requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678 Biotechnology Advances 33 (2015) 666680 Corresponding author at: Department of Chemical Engineering, University of Waterloo, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada. Tel.: +1 519 888 4567x38605; fax: +1 519 888 4347. E-mail address: frank.gu@uwaterloo.ca (F.X. Gu). http://dx.doi.org/10.1016/j.biotechadv.2015.03.003 0734-9750/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Biotechnology Advances journal homepage: www.elsevier.com/locate/biotechadv