General Strategy for Biodetection in High Ionic Strength Solutions Using Transistor-Based Nanoelectronic Sensors

Abstract

Transistor-based nanoelectronic sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although the short Debye screening length in high ionic strength solutions has made difficult applications relevant to physiological conditions. Here, we describe a new and general strategy to overcome this challenge for field-effect transistor (FET) sensors that involves incorporating a porous and biomolecule permeable polymer layer on the FET sensor. This polymer layer increases the effective screening length in the region immediately adjacent to the device surface, and thereby enables detection of biomolecules in high ionic strength solutions in real-time. Studies of silicon nanowire (SiNW) field-effect transistors (FETs) with additional polyethylene glycol (PEG) modification show that prostate specific antigen (PSA) can be readily detected in solutions with phosphate buffer (PB) concentrations as high as 150 mM, while similar devices without PEG modification only exhibit detectable signals for concentrations ≤ 10 mM. Concentration-dependent measurements exhibited real-time detection of PSA with a sensitivity of at least 10 nM in ~130 mM ionic strength PB with linear response up to the highest (1000 nM) PSA concentrations tested. The current work represents an important step toward general application of nanoelectronic detectors for biochemical sensing in physiological environments, and is expected to open up exciting opportunities for in-vitro and in-vivo biological sensing relevant to basic biology research through medicine.

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

“…2D). These results are consistent with previous observations for PEG-modified silicon nanowire FETs (25), and moreover, an estimate of the effective dielectric constant of the PEG layer (SI Text) supports the hypothesis that this permeable layer reduces the effective dielectric constant at sensor surface compared with aqueous solution.…”

“…In contrast, PEG/ETA-modified devices show only a gradual decrease in PSA-sensing signal with increasing PB concentration. The signal response in 100 mM PB, ∼14 mV, exceeds the signal recorded from ETA-modified devices in 10 mM PB, and moreover, well-defined sensing signals, ∼11 mV, can still be recorded in 150 mM PB where the Debye length is ∼0.5 nm (25). In addition, these data show that PSA sensing is reversible with the device conductance returning to baseline following addition of pure PB buffer, thus establishing that there is minimal irreversible protein binding to the modified graphene devices.…”

“…Recently, we have developed a strategy to overcome the Debye screening limitation that involves modification of a FET sensor surface with a biomolecule-permeable polymer layer to increase the effective screening length in the region immediately adjacent to the device, and demonstrated this concept for nonspecific detection of PSA using silicon nanowire sensors in physiological solutions (25). To explore the generality of this approach for nanomaterials-based FET sensors and further extend the concept to selective analyte recognition and detection, we herein describe studies demonstrating controlled nonspecific and highly selective protein detection in physiological media using graphene FET sensors in which the device surfaces are modified only with a biomolecule-permeable polymer layer and comodified with DNA aptamer/biomolecule-permeable polymer layer, respectively.…”

Sensing at the Surface of Graphene Field‐Effect Transistors

“…I). [74][75][76][77]80] At the end of this review, we will discuss in details that recent progresses on operating GFETs at high frequencies suggested that Debye screening can be overcome: [46] 1.…”

“…Possible routes to circumvent the Debye screening effect include short antibody design, porous polymer incorporation, and ex situ measurement in low ionic strength buffers (see Section 2.5). [74][75][76][77]80] These approaches, however, also impose limitations on the biodetection and it is highly desirable to develop a straightforward methods to overcome the Debye screening: [46] 1. without any special design or engineering of the receptor molecules and the sensor environments, and 2. in physiological conditions to facilitate in-situ, real-time biosensing. Theoretically, improved sensitivity is expected at high frequencies using a measuring strategy that overcomes the ionic screening effect.…”