The Virus Bioresistor: Wiring Virus Particles for the Direct, Label-Free Detection of Target Proteins

Abstract

The virus bioresistor (VBR) is a chemiresistor that directly transfers information from virus particles to an electrical circuit. Specifically, the VBR enables the label-free detection of a target protein that is recognized and bound by filamentous M13 virus particles, each with dimensions of 6 nm ( w) × 1 μm ( l), entrained in an ultrathin (∼250 nm) composite virus-polymer resistor. Signal produced by the specific binding of virus to target molecules is monitored using the electrical impedance of the VBR: The VBR presents a complex impedance that is modeled by an equivalent circuit containing just three circuit elements: a solution resistance ( R), a channel resistance ( R), and an interfacial capacitance ( C). The value of R, measured across 5 orders of magnitude in frequency, is increased by the specific recognition and binding of a target protein to the virus particles in the resistor, producing a signal Δ R. The VBR concept is demonstrated using a model system in which human serum albumin (HSA, 66 kDa) is detected in a phosphate buffer solution. The VBR cleanly discriminates between a change in the electrical resistance of the buffer, measured by R, and selective binding of HSA to virus particles, measured by R. The Δ R induced by HSA binding is as high as 200 Ω, contributing to low sensor-to-sensor coefficients-of-variation (<15%) across the entire calibration curve for HSA from 7.5 nM to 900 nM. The response time for the VBR is 3-30 s.

Phage-Based Sensors in Medicine: A Review

“…The good parameters of VBR ( Figure 8) described above and a satisfying LOD as low as 100 nM show promise for utilization of that sensor in clinical investigations. Even better properties (higher signal-to-noise ratio, lower response time) were achieved for the next VBR sensor described by Bhasin et al [60]. In their work, some improvements were applied, such as virus-PEDOT layer parameters.…”

Phage-based Electrochemical Sensors: A Review

“…With the phage display techniques, different proteins or peptides providing specific binding affinity to target molecules can be displayed on the phage surface. These genetically engineered phages could be used for biosensing of many other analytes, including glucose [91,92], cancer cells [93] and antibodies [62,[94][95][96][97][98][99][100][101][102]. [91].…”

“…The developed biosensors provided a much lower limit of detection as 100 pM for PSMA in synthetic urine without any amplification method [97]. The group further developed virus-based electrochemical biosensors for detection of human serum albumin (HSA) [98,99]. The virus-PEDOT films were synthesized as described in their previous works [95,96] and electropolymerized onto the gold electrodes, serving as the bio-recognition element.…”

“…The developed biosensors can detect HSA in the concentration range from 10 −7 to 5 × 10 −6 M within 15 min [98]. More recently, this group also proposed a virus bioresistor (VBR) that can directly transfer the binding of HSA to electric impedance signals as illustrated in Figure 4a [99]. The working principle was the same as in [98].…”

“…The proposed virus bioresistor (VBR) for human serum albumin (HAS) detection[99]: (a) compared to the buffer solution, the presence of target HSA will result in the increase of R VBR and (b) the sensing signal ∆R VBR was used for quantitative analysis of various HSA concentrations. The figures were adapted with permission from[99].…”