Investigation of Mechanisms Involved in the Enhanced Label Free Detection of Prostate Cancer Biomarkers Using Field Effect Devices

Abstract

This paper presents an experimental investigation on the effect of pH sensitivity of the dielectric surface in field effect based sensors on the label free detection of prostate specific antigen (PSA). Two types of electrolyte-insulator-semiconductor (EIS) devices using covalently attached antibodies were used in this study; a device with low pH sensitivity showed ∼63 mV flatband voltage shift while a device with relatively higher pH sensitivity showed ∼23 mV shift with a PSA concentration of 10 ng/ml in buffer. These observations validated the reported theoretical models, and reconciled the other reported experimental observations using adsorbed antibodies. The effects of different steps of surface modifications using aqueous solutions to covalently attach the antibodies were investigated to understand governing mechanisms responsible for enhanced PSA detection with the device with low pH sensitivity. The variations in the flatband voltages, contact angles, and pH sensitivities confirmed the tunability of the low pH sensitive devices upon any charge associated with the biomolecules (PSA). The learning from this study could be utilized to enhance the sensitivity of conventional ISFET biosensors and more specifically that of devices with non-silicon based semiconductors as the chemical functionalization processes significantly affect their performance.

Capacitive Field-Effect EIS Chemical Sensors and Biosensors: A Status Report

“…This way, the coupling of charged molecules, nanoparticles, and even inorganic/organic nanohybrids onto capacitive field-effect sensors is a very promising strategy to actively tune their electrochemical properties, especially with regards to label-free biosensing. Recent examples towards the label-free, direct electrical detection with the help of capacitive EIS sensors consider various kinds of charged molecules [ 7 , 27 , 130 , 131 , 132 ] and charged nanoobjects (nanoparticles and nanotubes) [ 112 , 113 , 133 , 134 ]. In this section, key developments of label-free EIS biosensors will be introduced, which mainly focus on electrostatic DNA detection, the detection of proteins, and oppositely charged PE macromolecules; all of them are monitored by their intrinsic molecular charge.…”

“…In contrast, no significant voltage shift in the C – V curve was detected by measurements in a solution with an ionic strength of 10 mM, which was attributed to the counter-ion screening effect of the PSA charge. In a further work, PSA antigens were immobilized onto a polyethyleneimine-modified SiO 2 -gate surface, resulting in enhanced sensitive properties [ 131 ]. The sensitivity toward PSA molecules in a low-ionic strength solution was 28.2 mV/dec and 4.7 mV/dec in the PSA concentration range of 1–10 ng/mL and 10 pg/mL–1 ng/mL, respectively.…”

Surface Charge Modulation and Reduction of Non-Linear Electrolytic Screening in FET-Based Biosensing

“…Hence, as already concluded by Wunderlich et al [6] "a quantitative detection of charged molecules by FETs is best achieved on surfaces with both low pH sensitivity and low surface potential". The negative correlation between pH sensitivity and bio-sensitivity has recently been observed experimentally [27].…”

Capacitive Field-Effect Biosensor Studying Adsorption of Tobacco Mosaic Virus Particles

“…Therefore, in principle, EIS sensors are able to detect the adsorption of charged macromolecules or nanoparticles onto the gate surface, since they are carrying an intrinsic molecular charge. This label-free detection principle has been demonstrated by different kinds of EIS sensors, e.g., for the label-free electrostatic detection of DNA immobilization and hybridization, biomarkers, polyelectrolytes, charged gold nanoparticles and carbon nanotubes [ 49 , 53 , 54 , 55 , 56 ]. In solution, virus particles are electrically charged.…”