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.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for almost 2 years. Stemming its spread has posed severe challenges for clinical virus detection. A long turnaround time, complicated operation, and low accuracy have become bottlenecks in developing detection techniques. Adopting a direct antigen detection strategy, we developed a fast-responding and quantitative capacitive aptasensor for ultratrace nucleocapsid protein detection based on a low-cost microelectrode array (MEA) chip. Employing the solid–liquid interface capacitance with a sensitivity of picofarad level, the tiny change on the MEA surface can be definitively detected. As a result, the limit of detection reaches an ultralow level of femtogram per milliliter in different matrices. Integrated with efficient microfluidic enrichment, the response time of this sensor from the sample to the result is shortened to 15 s, completely meeting the real-time detection demand. Moreover, the wide linear range of the sensor is from 10 –5 to 10 –2 ng/mL, and a high selectivity of 6369:1 is achieved. After application and evaluation in different environmental and body fluid matrices, this sensor and the detection method have proved to be a label-free, real-time, easy-to-operate, and specific strategy for SARS-CoV-2 screening and diagnosis.

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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