Abstract
In this paper, we demonstrate the possibility of direct protein sensing beyond the Debye length limit using a molecular-charge-contact (MCC)-based ion-sensitive field-effect transistor (ISFET) sensor combined with a microfluidic device. Different from the MCC method previously reported, biotin-coated magnetic beads are set on the gate insulator of an ISFET using a button magnet before the injection of target molecules such as streptavidin. Then, the streptavidin—a biotin interaction, used as a model of antigen—antibody reaction is expected at the magnetic beads/gate insulator nanogap interface, changing the pH at the solution/dielectric interface owing to the weak acidity of streptavidin. In addition, the effect of the pH or ionic strength of the measurement solutions on the electrical signals of the MCC-based ISFET sensor is investigated. Furthermore, bound/free (B/F) molecule separation with a microfluidic device is very important to obtain an actual electrical signal based on the streptavidin–biotin interaction. Platforms based on the MCC method are suitable for exploiting the advantages of ISFETs as pH sensors, that is, direct monitoring systems for antigen–antibody reactions in the field of in vitro diagnostics.
Highlights
A solution-gate ion-sensitive field-effect transistor (ISFET) was proposed for detecting ions in biological environments [1]
A problem of biologically coupled gate FET (bio-FET) sensors has been that biomacromolecules such as proteins cannot be detected using probe-tethered gate ISFET sensors because their charges are shielded by counter ions in sample solutions
The Debye screening effect on the biotin—streptavidin interaction at the sensor substrate was investigated previously [24], showing that the electrical signal of nanowire-FET devices was suppressed by the Debye screening in a 1X PBS solution, compared with that in the diluted buffer 0.01X PBS solution
Summary
A solution-gate ion-sensitive field-effect transistor (ISFET) was proposed for detecting ions in biological environments [1]. In this device, electrolyte solutions were assumed to induce the interfacial potential between the solution and the gate insulator instead of a metal gate in a metal-oxide-semiconductor (MOS) transistor, it was necessary to use a reference electrode in the solution. Electrolyte solutions include equal numbers of positive and negative ions, which results in a neutral solution. A deviation of the positive or negative charge density is found in the vicinity of the gate insulator depending on the density of the surface
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