Dual-Mode Electro-Optical Techniques for Biosensing Applications: A Review

Abstract

The monitoring of biomolecular interactions is a key requirement for the study of complex biological processes and the diagnosis of disease. Technologies that are capable of providing label-free, real-time insight into these interactions are of great value for the scientific and clinical communities. Greater understanding of biomolecular interactions alongside increased detection accuracy can be achieved using technology that can provide parallel information about multiple parameters of a single biomolecular process. For example, electro-optical techniques combine optical and electrochemical information to provide more accurate and detailed measurements that provide unique insights into molecular structure and function. Here, we present a comparison of the main methods for electro-optical biosensing, namely, electrochemical surface plasmon resonance (EC-SPR), electrochemical optical waveguide lightmode spectroscopy (EC-OWLS), and the recently reported silicon-based electrophotonic approach. The comparison considers different application spaces, such as the detection of low concentrations of biomolecules, integration, the tailoring of light-matter interaction for the understanding of biomolecular processes, and 2D imaging of biointeractions on a surface.

Keywords: electro-optical devices; label-free detection; optical biosensors.

Figure 1

Optical biosensors based on evanescent wave detection. The properties of the optical mode confined in a photonic substrate are sensitive to the overlap between the evanescent field and the surrounding environment. A change in the local refractive index, for example, due to formation of an antibody-antigen complex, leads to a change in the properties of the confined optical mode and to a quantifiable readout of molecular binding.

Figure 2

Schematic of surface plasmon resonance (SPR) field distribution at a metal-dielectric interface. The overlap of the evanescent field with the dielectric phase of the interface provides a direct measurement of changes in the local refractive index.

Figure 3

Schematic diagram of electrochemical-SPR (EC-SPR). The gold substrate that carries the optical surface mode is simultaneously used as the working electrode, allowing simultaneous optical and electrochemical interrogation. Typically, the fluidic manifold also includes counter and reference electrodes to form a complete three-electrode electrochemical cell.

Figure 4

Optical waveguide lightmode spectroscopy (OWLS) sensing mechanism. The incoupling angle varies as a function of the refractive index as experienced by the guided optical mode.

Figure 5

Electrochemical optical waveguide lightmode spectroscopy (EC-OWLS). The angle of light coupled into the waveguide by the grating depends on the refractive index of the molecules attached to the sensor surface while the indium tin oxide (ITO) provides an electrically conductive layer to support electrochemistry.

Figure 6

Electrophotonic silicon biosensing. (a) Cross section of an electrophotonic silicon biosensor. The electrochemical functionality is provided by doping the surface of the silicon waveguide layer; (b) Sketch of an electrophotonic silicon sensor based on a ring resonator structure.

Figure 7

Monitoring of conformational changes with electro-photonic silicon biosensing. (a) Single-stranded DNA is immobilised on the sensor surface. A redox active probe linked to the DNA oligonucleotide enables electrochemical measurement of DNA hybridisation; (b) Upon binding to its complementary strand, the surface-immobilised DNA strand undergoes a conformational change, displacing the electrochemical probe away from the surface. This modifies the thermodynamics of the electron-transfer process, hence exhibiting changes in the electrochemical response. This conformational change can simultaneously be monitored in real-time and quantified using the underlying silicon photonic sensor.