title: A nanoelectronic enzyme-linked immunosorbent assay for detection of proteins in physiological solutions.
abstract: Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field-effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening. A general solution to this limitation with the development of a hybrid nanoelectronic enzyme-linked immunosorbent assay (ne-ELISA) that combines the power of enzymatic conversion of a bound substrate with electronic detection is demonstrated. This novel configuration produces a local enzyme-mediated pH change proportional to the bound ligand concentration. It is shown that nanowire FETs configured as pH sensors can be used for the quantitative detection of interleukin-2 in physiologically buffered solution at concentrations as low as 1.6 pg mL(-1). By successfully bypassing the Debye screening inherent in physiological fluids, the ne-ELISA promises wide applicability for ligand detection in a range of relevant solutions.
authors.affiliation: Departments of Electrical, Biomedical, and Chemical Engineering, and Applied Physics, School of Engineering, Yale University, New Haven, CT 06511, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Stern
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vacic
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Fumiaki N
authors.initials: FN
authors.lastname: Ishikawa
authors.forename: Chongwu
authors.initials: C
authors.lastname: Zhou
authors.forename: Mark A
authors.initials: MA
authors.lastname: Reed
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Fahmy
mesh_terms: D004563:Electrochemistry; D004583:Electrons; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000032:analysis*; D053770:Nanowires / Q000737:chemistry* / Q000648:ultrastructure; D012996:Solutions
chemical_list: D007376:Interleukin-2; D012996:Solutions