Impedimetric and potentiometric biosensors have attracted considerable attention due to high sensitivity, high selectivity, rapid response time, low cost as well as miniaturization, and large numbers of them have been applied in the fields of pH detection, DNA detection, protein detection, cell analysis etc. However, compared with potentiometric field-effect transistor (FET) biosensors, impedimetric biosensors have the disadvantage of lower selectivity and they can not directly perform real-time detection. Meanwhile, there are still some limitations and challenges which have restricted the performance of FET-based biosensors at this moment, such as the limitation of Debye length screening. Based on the current development, this dissertation designed, fabricated and characterized...[ Read more ]

Impedimetric and potentiometric biosensors have attracted considerable attention due to high sensitivity, high selectivity, rapid response time, low cost as well as miniaturization, and large numbers of them have been applied in the fields of pH detection, DNA detection, protein detection, cell analysis etc. However, compared with potentiometric field-effect transistor (FET) biosensors, impedimetric biosensors have the disadvantage of lower selectivity and they can not directly perform real-time detection. Meanwhile, there are still some limitations and challenges which have restricted the performance of FET-based biosensors at this moment, such as the limitation of Debye length screening. Based on the current development, this dissertation designed, fabricated and characterized the impedimetric and FET-based biosensors for biomolecule detection with high performance.

An impedimetric polymer-based micro electrochemical sensor (PMES) was designed and fabricated to achieve rapid, label-free and cost-effective DNA detection. The relationship between device dimension and PMES’s sensitivity was studied, which revealed that the PMES with smallest dimension has shown best performance. The PMES chip has realized effective and rapid detection of DNA concentration with the sensitivity of 3.77 kΩ/nM and limit of detection (LOD) of 10 nM by the electrochemical impedance spectroscopy (EIS). Moreover, rapid label-free detection of Cordyceps sinensis (CorS) based on DNA hybridization by the PMES chip with the sensitivity of 7.94 kΩ/nM (2.48 kΩ·μl/ng) and the LOD of 720 pM (2.3 ng/μl) was successfully achieved.

A dual-gate nanoribbon-based ion-sensitive field-effect transistor (NR-ISFET) biosensor for direct label-free DNA detection with high sensitivity was successfully designed, simulated and fabricated. Real-time conductance measurements of the NR-ISFET biosensors with different sample delivery configuration including a cavity and microchannel were conducted in solution-gate (SG) and dual-gate (DG) working modes. It reveals that the performance of NR-ISFET biosensor system was enhanced by using a microchannel as compared to a cavity due to better surface modification and enhanced mass transport. By using a microchannel for sample delivery, the NR-ISFET biosensor in DG mode exhibited LOD of 50 pM and sensitivity of 0.5054 mS/dec in a wide working range spanning four orders of magnitude, and significantly improve specificity compared with these in SG mode. According to the simulation and experimental results, the enhancement of sensor sensitivity and reduction of LOD can be attributed to the application of back gate.

A polyethylene glycol (PEG)-modified dual-gate NR-ISFET biosensor was designed and fabricated for direct, label-free and real-time protein detection in high ionic strength solution and human plasma with high sensitivity and high specificity. The application of PEG modification increased the effective Debye length, which enabled the direct protein detection in high ionic strength solution and human plasma. The incorporation of specific antibody can realize the selective protein detection. The direct detection of prostate specific antigen (PSA) in 100 mM phosphate buffer (PB) solution based on antibody-antigen binding ranging from 10 pM to 1 μM was achieved by the NR-ISFET biosensor in DG mode without prior desalting. More significantly, direct real-time specific detection of PSA of 100 pM to 1 μM in human plasma by the NR-ISFET biosensor in DG mode was successfully demonstrated, which has met the clinical requirements for minimum PSA concentration of human body less than 120 pM.

Finally, planar and gate-recessed AlGaN/GaN high electron mobility transistor (HEMT) biosensors were designed, fabricated and characterized for pH detection with high sensitivity. The effect of recess depth on the biosensor performance including pH sensitivity, maximum transconductance and maximum saturation current was investigated. Based on the simulation and experimental results, the AlGaN/GaN HEMT biosensor performance was significantly enhanced when the recess depth increased. The pH sensitivity has improved from 31.3 mV/pH to 50.1 mV/pH when the recess depth increased from 0 nm to 15 nm, which was much larger than that of previously mentioned Si-based NR-ISFET biosensors (29.3 mV/pH).

In conclusion, high performance impedimetric and FET-based biosensors were designed, fabricated and characterized in this work, which have achieved the detection of different biomolecules and overcome the challenge of Debye length screening.