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Conventional affinity biosensor typically relies on passive diffusion of analytes for binding reaction, which in many cases leads to long response time and lack of sensitivity. Recent research showed that directed particle motion towards sensor electrodes could be induced in sample matrix by applying an inhomogeneous AC electric field, often with AC dielectrophoresis as the responsible mechanism. As a result, shorter assay time and higher sensitivity can be achieved. Previously, we demonstrated a rapid and sensitive AC capacitive affinity sensor, which integrates low voltage AC dielectrophoresis into label-free capacitive measurement to achieve a single-step operation without any wash steps for clinical samples. However, dielectrophoretic force is rather short-ranged, and is also proportional to the size of target biomolecules/particles. Therefore, to detect target molecule at diluted concentrations or small molecule, improvement in sensitivity by dielectrophoresis could be quite limited. Alternatively, AC electric field can also produce microfluidic movement to carry biomolecules to sensors, which is of long range and size independent. This work demonstrates the use of low voltage AC electrothermal effect to enhance and accelerate the detection of low abundance and small target molecules by AC capacitive sensing with simultaneous AC electrokinetic enrichment. Electrode designs were studied for their effectiveness in AC electrothermal capacitive sensing. Electrodes with larger characteristic length were found to be more amenable to inducing AC electrothermal convection and were successfully used to detect low abundance protein and femto-molar level small molecules.

This work presents an AC electrokinetic impedance sensing method that is capable of detecting specific interactions between macromolecules such as antigen-antibody binding. Serum samples were added to the surface of interdigitated electrodes that had been coated with bacterial antigens. After applying an AC signal of 100 mV at a specific frequency continuously, the electrodes' impedance change was recorded and used to determine the occurrence and level of antibody binding to the antigen. Our theoretical analysis indicated that with this AC signal, the target macromolecules will experience a sufficiently strong attraction force towards the electrode surface for acceleration of the binding process. Using this method, 11 human tuberculosis and 10 bovine tuberculosis serum samples were tested. The results were consistent with those obtained by a conventional ELISA method. The limit of detection of the impedance sensing method was estimated to be better than 10 ng mL(-1). In summary, we demonstrate that AC electrokinetic impedance sensing can be used for rapid and sensitive detection of specific antibodies in serum samples. This method may form a basis for development of a point of care diagnostic device for human and bovine tuberculosis.

Bisphenol A (BPA) is an endocrine disrupting compound that may have adverse developmental, reproductive, neurological, and immune system effects. Low-level exposure to BPA is ubiquitous in human populations due to its widespread use in consumer products. Therefore, highly sensitive methods are needed to quantify BPA in various matrices including water, serum, and food products. In this study, we developed a simple, rapid, highly sensitive and specific sensor based on an aptamer probe and AC electrokinetics capacitive sensing method that successfully detected BPA at femto molar (fM) levels, which is an improvement over prior work by a factor of 10. We were able to detect BPA spiked in human serum as well as in maternal and cord blood within 30s. The sensor is responsive to BPA down to femto molar levels, but not to structurally similar compounds including bisphenol F (BPF) or bisphenol S (BPS) even at much higher concentration. Further development of this platform may prove useful in monitoring exposure to BPA and other small molecules in various matrices.

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