title: Label-free histamine detection with nanofluidic diodes through metal ion displacement mechanism.
abstract: We design and characterize a nanofluidic device for the label-free specific detection of histamine neurotransmitter based on a metal ion displacement mechanism. The sensor consists of an asymmetric polymer nanopore fabricated via ion track-etching technique. The nanopore sensor surface having metal-nitrilotriacetic (NTA-Ni2+) chelates is obtained by covalent coupling of native carboxylic acid groups with Nα,Nα-bis(carboxymethyl)-l-lysine (BCML), followed by exposure to Ni2+ion solution. The BCML immobilization and subsequent Ni2+ion complexation with NTA moieties change the surface charge concentration, which has a significant impact on the current-voltage (I-V) curve after chemical modification of the nanopore. The sensing mechanism is based on the displacement of the metal ion from the NTA-Ni2+chelates. When the modified pore is exposed to histamine solution, the Ni2+ion in NTA-Ni2+chelate recognizes histamine through a metal ion coordination displacement process and formation of stable Ni-histamine complexes, leading to the regeneration of metal-free NTA groups on the pore surface, as shown in the current-voltage characteristics. Nanomolar concentrations of the histamine in the working electrolyte can be detected. On the contrary, other neurotransmitters such as glycine, serotonin, gamma-aminobutyric acid, and dopamine do not provoke significant changes in the nanopore electronic signal due to their inability to displace the metal ion and form a stable complex with Ni2+ion. The nanofluidic sensor exhibits high sensitivity, specificity and reusability towards histamine detection and can then be used to monitor the concentration of biological important neurotransmitters.
authors.affiliation: Technische Universität Darmstadt, Fachbereich Material- u. Geowissenschaften, Fachgebiet Materialanalytik, Alarich-Weiss-Str. 2, D-64287 Darmstadt, Germany; GSI Helmholtzzentrum für Schwerionenforschung, Planckstr. 1, D-64291 Darmstadt, Germany. Electronic address: M.Ali@gsi.de.
authors.forename: Mubarak
authors.initials: M
authors.lastname: Ali
authors.affiliation: Departament de Física Aplicada, Universitat Politécnica de València, E-46022 València, Spain.
authors.forename: Patricio
authors.initials: P
authors.lastname: Ramirez
authors.affiliation: Technische Universität Darmstadt, Fachbereich Material- u. Geowissenschaften, Fachgebiet Materialanalytik, Alarich-Weiss-Str. 2, D-64287 Darmstadt, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Duznovic
authors.affiliation: Technische Universität Darmstadt, Fachbereich Material- u. Geowissenschaften, Fachgebiet Materialanalytik, Alarich-Weiss-Str. 2, D-64287 Darmstadt, Germany.
authors.forename: Saima
authors.initials: S
authors.lastname: Nasir
authors.affiliation: Departament de Física de la Terra i Termodinàmica, Universitat de València, E-46100 Burjassot, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Mafe
authors.affiliation: Technische Universität Darmstadt, Fachbereich Material- u. Geowissenschaften, Fachgebiet Materialanalytik, Alarich-Weiss-Str. 2, D-64287 Darmstadt, Germany; GSI Helmholtzzentrum für Schwerionenforschung, Planckstr. 1, D-64291 Darmstadt, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ensinger
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D004553:Electric Conductivity; D004566:Electrodes; D004952:Esters; D006632:Histamine / Q000737:chemistry*; D006868:Hydrolysis; D007477:Ions / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D008962:Models, Theoretical; D058608:Nanopores; D036103:Nanotechnology / Q000379:methods; D018377:Neurotransmitter Agents / Q000737:chemistry; D009532:Nickel / Q000737:chemistry; D009571:Nitrilotriacetic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties
chemical_list: D002264:Carboxylic Acids; D002614:Chelating Agents; D004952:Esters; D007477:Ions; D008670:Metals; D018377:Neurotransmitter Agents; D011108:Polymers; D009532:Nickel; D006632:Histamine; D009571:Nitrilotriacetic Acid
keywords: Histamine; NTA-metal complex; Nanofluidic sensor; Neurotransmitter; Surface functionalization