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 field-effect transistors 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 100 mM PB with linear response up to the highest (1000 nM) PSA concentrations tested. The current work represents an important step toward general application of transistor-based 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.

Keywords: Debye length; Semiconductor nanowires; bioelectronics; field-effect-transistor; polyethylene glycol; polymer-modified.

Figure 1. Polymer surface modification to increase the effective Debye length for FET biosensing

(a) Schematic illustration of a NW FET device (top) without and (bottom) with a porous and biomolecule permeable polymer (green) surface modification. The magenta features on both NW surfaces represent APTES in these studies, or more generally, specific receptors. (b) Optical image of device chip (central light purple square, ca. 2 × 2 cm²) mounted on a PCB interface board that is plugged into the input/output interface connected (left side of image) to a computer controlled data acquisition system (not shown). The copper squares surrounding the device chip are connected to the chip by wire-bonding (not visible). A poly(dimethylsiloxane) (PDMS)-based microfluidic channel is mounted over the central SiNW device region of the chip with solution input/output via tubing (translucent, center to upper left/right of image) during real-time biosensing experiments. The inset shows a bright-field microscopy image of a portion of device chip containing 18 of 188 total FET devices on the chip; scale bar is 40 μm. Metal lines are visible in the image with common source (S) and one addressable drain (D) electrode labeled; the other addressable D electrodes are visible as the thin gold colored lines oriented upwards and downwards to right. The blue arrow highlights one SiNW FET as shown schematically in (a).

Figure 2. Real-time PSA detection using SiNW FETs sensors with and without PEG surface modifications

(a) Signal amplitude vs time data recorded from an APTES modified SiNW FET following addition of 100 nM PSA (black arrow) and pure buffer (initial and following green arrow) for different pH 6 PB concentrations. (b) – (d) Comparison of signal response traces recorded simultaneously from three SiNW FET devices following addition of 100 nM PSA in different concentration pH 6 PBs; the devices were modified with 4 : 1 APTES/silane-PEG. The PB concentrations of the pure and PSA/PB solutions in (b), (c) and (d) were 50, 100 and 150 mM, respectively. Black and green arrows in figure correspond to the points where the solution flow was switched from pure buffers to protein solutions and from protein solutions to pure buffers; the delay from solution switch to signal change corresponds to the time for solution to flow from the entry point to the devices in our set-up.

Figure 3. Reproducible PSA detection by FET sensors in high ionic strength solutions

(a) Comparison of PSA response signals from independent sensor chips as labeled in the figure, where APTES/PEG corresponds to modification with 4 : 1 APTES/silane-PEG as described in the text. The error bars for each experiment correspond to ± 1 standard deviation from data acquired simultaneously from three independent devices. (b) The dependence of PSA signal amplitudes and Debye length on the PB concentrations. The SiNW FET functionalization is the same as in (a).

Figure 4. Concentration-depended PSA detection in high ionic strength solutions

(a) Time-dependent signal response traces at different PSA concentrations for a PEG-modified SiNW FET sensor in pH6 100 mM PB. (b) Plot of the sensor response vs PSA concentration. The red line is fit of the data with Langmuir adsorption isotherm with k = 6.4 ×10⁶ M⁻¹. The inset shows sensor response (conductance change) versus logarithm of the PSA concentration.