Rapid detection of bladder cancer using an immunoassay transistor combined with DNA-labeling technique in a microfluidic chip

We propose a method that can be used to quantitatively measure concentrations of protein through a semiconductor sensor with a robust signal. Measurement of protein by a semiconductor may encounter a major problem. For specifically measuring protein, an antibody is immobilized on the semiconductor sensor surface. The physical length of the antibody is around 10 nm, a distance too long to be sensed by the semiconductor sensor, which means that the following attached protein cannot be sensed. In this study, we used a bead-based immunoassay combined with the DNA strain labeling technique to overcome this issue. Protein was first captured using an antibody-coated magnetic bead. It was then labeled with a secondary antibody combined with the DNA strain. Finally, the magnetic bead with the biotarget was attracted on the sensor surface by an external magnetic field, and then the negative charges of the DNA changed the surface potential of the sensor. The concentration of protein could then be measured accordingly. The signal could be further improved by the optimization of the number of labeling DNA and the size of the magnetic bead. In addition, the semiconductor sensor was incorporated in a microfluidic chip with microvalves and a micromixer. The microfluidic procedure reduced the total measurement time to around 1 h (plate ELISA 4h). Furthermore, by changing the antibody to another type of antibody coated on the magnetic bead, the sensor could be reused to measure other types of protein. The proposed method provides a solution for the robust measurement of protein concentration through the semiconductor sensor.