title: Ultrasensitive multiplex optical quantification of bacteria in large samples of biofluids.
abstract: Efficient treatments in bacterial infections require the fast and accurate recognition of pathogens, with concentrations as low as one per milliliter in the case of septicemia. Detecting and quantifying bacteria in such low concentrations is challenging and typically demands cultures of large samples of blood (~1 milliliter) extending over 24-72 hours. This delay seriously compromises the health of patients. Here we demonstrate a fast microorganism optical detection system for the exhaustive identification and quantification of pathogens in volumes of biofluids with clinical relevance (~1 milliliter) in minutes. We drive each type of bacteria to accumulate antibody functionalized SERS-labelled silver nanoparticles. Particle aggregation on the bacteria membranes renders dense arrays of inter-particle gaps in which the Raman signal is exponentially amplified by several orders of magnitude relative to the dispersed particles. This enables a multiplex identification of the microorganisms through the molecule-specific spectral fingerprints.
authors.affiliation: Universitat Rovira i Virgili and Centro de Tecnología Química de Catalunya, Carrer de Marcel·lí Domingo s/n, 43007 Tarragona, Spain.|Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pazos-Perez
authors.affiliation: Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Pazos
authors.affiliation: Universitat Rovira i Virgili and Centro de Tecnología Química de Catalunya, Carrer de Marcel·lí Domingo s/n, 43007 Tarragona, Spain.|Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Catala
authors.affiliation: Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.|Department of Surgery, UD-Vall d'Hebron School of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Mir-Simon
authors.affiliation: Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Gómez-de Pedro
authors.affiliation: Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sagales
authors.affiliation: Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.|Department of Surgery, Hospital el Pilar, 08006 Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Villanueva
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic and School of Medicine, University of Barcelona, Barcelona, Spain.|Barcelona Center for International Health Research (CRESIB), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Department of Infectious Diseases, Hospital Clínic and School of Medicine, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Soriano
authors.affiliation: ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.|ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: García de Abajo
authors.affiliation: Universitat Rovira i Virgili and Centro de Tecnología Química de Catalunya, Carrer de Marcel·lí Domingo s/n, 43007 Tarragona, Spain.|Medcom Advance S.A., Av. Roma, 08840 Barcelona, Spain.|ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Alvarez-Puebla
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D001419:Bacteria / Q000737:chemistry* / Q000302:isolation & purification; D001826:Body Fluids / Q000382:microbiology*; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D044085:Microfluidics / Q000379:methods; D046529:Microscopy, Electron, Transmission; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D012834:Silver / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013291:Streptococcus / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D012834:Silver