Rapid and sensitive detection of small biomolecule by capacitive sensing and low field AC electrothermal effect

Abstract

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 a non-uniform 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.