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This work explores Electrochemical Impedance Spectroscopy (EIS) detection for a highly-sensitive quantification of prostate-specific antigen (PSA) in Faradaic (f-EIS) and non-Faradaic modes (nf-EIS). Immobilization of monoclonal antibody specific to PSA (anti-PSA) was performed using 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and N-hydroxysuccinimide crosslinking agents in order to conjugate carboxylic (-COOH) terminated group of 16-Mercaptoundecanoic acid with amine (-NH3+) on anti-PSA epitope. This approach offers simple and efficient approach to form a strong, covalently bound thiol-gold (S Au) for a reliable SAM layer formation. Studies on the topographic of pristine Au-IDE surface were performed by Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy techniques, meanwhile a 3-dimensional optical surface profiler, Atomic Force Microscopy and X-ray Photoelectron Spectroscopy techniques were used to validate the successful functionalization steps on the sensor transducer surface. Detection of PSA in f-EIS mode was carried out by measuring the response in charge transfer resistance (Rct) and impedance change (Z), meanwhile in nf-EIS mode, the changes in device capacitance was monitored. In f-EIS mode, the sensor reveals a logarithmic detection of PSA in a range of 100 ng/ml down to 0.01 ng/ml in Phosphate Buffered Saline with a recorded sensitivity of 2.412 kΩ/log10 ([PSA] ng/ml) and the limit of detection (LOD) down to 0.01 ng/ml. The nf-EIS detection mode yields a logarithmic detection range of 5000 ng/ml down to 0.5 ng/ml, with a sensitivity of 8.570 nF/log10 ([PSA] ng/ml) and an LOD of 0.5 ng/ml. The developed bio-assay yields great device stability, specificity to PSA and repeatability of detection that would pave its way for the future development into portable lab-on-chip bio-sensing system.

Field-effect transistor biosensors have attracted tremendous interests in the field of diagnosis due to their appealing characteristics such as high sensitivity, label-free detection and low-cost. In addition, their compatibility with the existing complementary metal oxide semiconductor technology has made them feasible for miniaturization, standardization, mass production and integration of readout circuitry compared to other bio-sensing technologies. Coupled with additional voltage biasing, FET prevails its versatility in terms of electrical modulation i.e. ambipolar conduction (holes or electrons that depend on additional voltage biasing). In this work, the field-effect transistor based biosensor was fabricated by using the silicon-on-insulator wafer. To utilize the sensing area, the titanium dioxide thin film was deposited on the channel area, in-between the source and drain. The atomic force microscopy, scanning electron microscopy, and X-ray diffraction were used to characterize the physical structure of the device and TiO2 anatase thin film. The surface functionalized specific functional groups were determined by using the Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Finally, the electrical characteristic with back-gate biasing was conducted for the detection of cardiac troponin I. It was observed that the significant amplification signal with back-gate biasing of −3 V with the detection limit of 0.238 ng/ml and increased sensitivity to 2.438 μA(g/ml)−1 can be achieved with ambipolar conduction. This brings to a conclusion that the back-gated field-effect transistor is a promising approach for enhancing the sensitivity of the FET-based biosensors.

Currently, field-effect transistor (FET)-based biosensors have been implemented in several portable sensors with the ultimate application in point-of-care testing (POCT). In this paper, we have designed substrate-gate coupling in FET-based biosensor for the detection of cardiac troponin I (cTnI) biomarker. In the device structure, zinc oxide nanoparticles (ZnO-NPs) thin film were deposited through sol-gel and spin coating techniques on the channel. The p-type silicon was used as a substrate, while ZnO is an n-type nanomaterial, thus creates p - n- p junction between source, channel, and drain. The deposited thin films exhibited hexagonal wurtzite phase of ZnO, suitable for biomolecular interaction as revealed in X-ray diffraction (XRD) analysis. The surface of the thin film was then functionalized with 3-aminopropyltriethoxysilane (APTES), followed by glutaraldehyde (GA) as a bi-functional linker to immobilize the cTnI monoclonal antibody (MAb-cTnI) as bio-receptor for capturing cTnI biomarker and proven by the Fourier transform-infrared (FT-IR) spectra. Lastly, we demonstrated a new strategy, the integration of FET-based biosensors with substrate-gate showed differences between before (immobilization) and after cTnI target biomarker interaction by significant changes in drain current (I D ) and change of threshold voltage (V T ), which improved the sensitive detection, with the limit of detection down to 3.24 pg/ml.

A simple, single-masked gold interdigitated triple-microelectrodes biosensor is presented by taking the advantage of an effective self-assembled monolayer (SAM) using an amino-silanization technique for the early detection of a prostate cancer's biomarker, the prostate-specific antigen (PSA). Unlike most interdigitated electrode biosensors, biorecognition happens in between the interdigitated electrodes, which enhances the sensitivity and limit of detection of the sensor. Using the Faradaic mode electrochemical impedance spectroscopy (EIS) technique to quantify the PSA antigen, the developed sensing platform demonstrates a logarithmic detection of PSA ranging from 0.5 ng/ml to 5000 ng/ml, an estimated LOD down to 0.51 ng/ml in the serum, and a good sensor's reproducibility. The sensor's detection range covers the clinical threshold value at 4 ng/ml and the crucial diagnosis ‘grey zone’ of 4–10 ng/ml of PSA in serum for an accurate cancer diagnosis. The selectivity test revealed an excellent discrimination of other competing proteins, with a recorded detection signals at 5 ng/ml PSA as high as 7-fold increase versus the human serum albumin (HSA) and 8-fold increase versus the human glandular kallikrein 2 (hK2). The stability test showed an acceptable stability of the aptasensor recorded at six (6) days before the detection signal started degrading below 10% of the peak detection value. The developed sensing scheme is proven to exhibit a great potential as a portable prostate cancer biosensor, also as a universal platform for bio-molecular sensing with the versatility to implement nanoparticles and other surface chemistry for various applications.

A real-time ability to interpret the interaction between targeted biomolecules and the surface of semiconductors (metal transducers) into readable electrical signals, without biomolecular modification involving fluorescence dyes, redox enzymes, and radioactive labels, created by label-free biosensors has been extensively researched. Field-effect transistor (FET)- and capacitor-based biosensors are among the diverse electrical charge biosensing architectures that have drawn much attention for having charge transduction; thus, enabling the early and rapid diagnosis of the appropriate cardiac biomarkers at lower concentrations. These semiconducting material-based transducers are very suitable to be integrated with portable electronic devices for future online collection, transmission, reception, analysis, and reporting. This overview elucidates and clarifies two major electrical label-free systems (FET- and capacitor-based biosensors) with cardiac troponin (cTn) biomarker-mediated charge transduction for acute myocardial infarction (AMI) diagnosis. Advances in these systems are highlighted by their progression in bridging the laboratory and industry; the foremost technologies have made the transition from benchtop to bedside and beyond.

The existing FET-based biosensors nowadays only depend on a physical structure size of a device. Due to those limitation, the device can only be read with the presence of high sensitivity electrical readers. To synchronize the device with a low-cost portable electrical reader, the electrical signal need to be amplified with minimal noise output. In this work, a label-free, specific and sensitive back-gated FET based biosensor is presented for the detection of cTnI protein by using SOI type of wafer with TiO 2 act as a transducer material. TiO 2 is deposited by using sol-gel method with surface functionalized for cTnI protein binding. From the XPS result, it shows that each covalent bonding characteristic from APTES deposition until cTnI antibody-antigen interaction. Finally, the electrical (I d -V bg ) result show the ability to detect cTnI protein with concentration of 2.0 µg/µl at −150 µA (V d = 0). As V d increases, a tremendous increment of electrical conductivity with larger difference of I d value between each surface functionalization processes can be achieved. At V d = −5, the electrical conductivity jumped up to −1 mA, more than 500% increase compared to V d = 0.