Label-free histamine detection with nanofluidic diodes through metal ion displacement mechanism

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 N_α,N_α-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.