Microelectrical sensors as emerging platforms for protein biomarker detection in point-of-care diagnostics

Abstract

Current methods used to measure protein expression on microarrays, such as labeled fluorescent imaging, are not well suited for real-time, diagnostic measurements at the point of care. Studies have shown that microelectrical sensors utilizing silica nanowire, impedimetric, surface acoustic wave, magnetic nanoparticle and microantenna technologies have the potential to impact disease diagnosis by offering sensing characteristics that rival conventional sensing techniques. Their ability to transduce protein binding events into electrical signals may prove essential for the development of next-generation point-of-care devices for molecular diagnostics, where they could be easily integrated with microarray, microfluidic and telemetry technologies. However, common limitations associated with the microelectrical sensors, including problems with sensor fabrication and sensitivity, must first be resolved. This review describes governing technical concepts and provides examples demonstrating the use of various microelectrical sensors in the diagnosis of disease via protein biomarkers.

Figure 1. The top impedance sensor has antibodies immobilized on top of and between the gold electrodes, while the bottom sensor also has bound antigens

Both sensors will have an aqueous solution covering the active region (interdigitated region) of the sensor. The bound antigens will change the resistance and capacitance of the sensor. The image to the right represents a top view of a sensor, which is an interdigitated circuit.

Figure 2. A SAW delay line consists of an IDT, an output IDT and a piezoelectric substrate

Two delay lines operate in parallel, with one line acting as a reference line and the other acting as an experimental line. A sinusoidal voltage is applied to the input IDT, which develops an alternating electric field that is translated into a mechanical SAW by the piezoelectric effect. The velocity of the SAW is affected by mass loading, fluid viscosity and temperature on the surface of the substrate. The reverse piezoelectric effect translates the SAW into an oscillating electric field at the output IDT. Any difference in velocity between the two delay lines would be reflected as a phase shift and amplitude difference. IDT: Input interdigitated transducer; SAW: Surface acoustic-wave.

Figure 3. Cross-sectional view of a Love mode surface acoustic-wave sensor (layer thicknesses not to scale) displaying the piezoelectric substrate, two IDTs, the waveguide layer and the sensing layer

The waveguide layer consists of either an oxide or polymer layer, which functions to trap the acoustic energy of the SAW at the interface between the waveguide and the substrate to minimize propagation losses. It also serves to protect the IDTs from corrosion, thus providing for measurements to be made in a liquid environment. The sensing layer provides for the capture and immobilization of the biological or chemical agent of interest to the active surface of the sensor in order to develop a detectable mass loading effect. IDT: Input interdigitated transducer.

Figure 4. The image to the right represents a top view of a microantenna sensor with a line representing a cross-section shown on the left

The upper sensor has antibodies immobilized on top of the active region of the antennas, while the lower sensor also has captured antigens. The shielded traces are on both sides of the transmitting and receiving antennas. Their presence should prevent signals from traveling in a direct path between antennas. The bound antigens should change the attenuation of the sensor because of the increased affected antenna height.