Yen Wen Chen

Beyond the Debye length in high ionic strength solution: direct protein detection with field-effect transistors (FETs) in human serum

In this study, a new type of field-effect transistor (FET)-based biosensor is demonstrated to be able to overcome the problem of severe charge-screening effect caused by high ionic strength in solution and detect proteins in physiological environment. Antibody or aptamer-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) are used to directly detect proteins, including HIV-1 RT, CEA, NT-proBNP and CRP, in 1X PBS (with 1%BSA) or human sera. The samples do not need any dilution or washing process to reduce the ionic strength. The sensor shows high sensitivity and the detection takes only 5 minutes. The designs of the sensor, the methodology of the measurement, and the working mechanism of the sensor are discussed and investigated. A theoretical model is proposed based on the finding of the experiments. This sensor is promising for point-of-care, home healthcare, and mobile diagnostic device.

High sensitivity cardiac troponin I detection in physiological environment using AlGaN/GaN High Electron Mobility Transistor (HEMT) Biosensors

In this study, we report the development of a high sensitivity assay for the detection of cardiac troponin I using electrical double layer gated high field AlGaN/GaN HEMT biosensor. The unique gating mechanism overcomes the drawback of charge screening seen in traditional FET based biosensors, allowing detection of target proteins in physiological solutions without sample processing steps. Troponin I specific antibody and aptamer are used as receptors. The tests carried out using purified protein solution and clinical serum samples depict high sensitivity, specificity and wide dynamic range (0.006-148ng/mL). No additional wash or sample pre-treatment steps are required, which greatly simplifies the biosensor system. The miniaturized HEMT chip is packaged in a polymer substrate and easily integrated with a portable measurement unit, to carry out quantitative troponin I detection in serum samples with < 2µl sample volume in 5min. The integrated prototype biosensor unit demonstrates the potential of the method as a rapid, inexpensive, high sensitivity CVD biomarker assay. The highly simplified protocols and enhanced sensor performance make our biosensor an ideal choice for point of care diagnostics and personal healthcare systems.

Unconventional interplay between heterovalent dopant elements: Switch-and-modulator band-gap engineering in (Y, Co)-Codoped CeO2 nanocrystals.

We report the experimental observation and theoretical explanation of an unconventional interplay between divalent Co and trivalent Y dopants, both of which incur oxygen vacancies in the CeO2 host that has predominantly tetravalent Ce cations. The Co dopant atoms were experimentally found to act as a switch that turns on the dormant effect of Y-modulated band-gap reduction. As revealed by density functional theory (DFT) calculations with structures verified by synchrotron-radiation x-ray measurements, a Co 3d band that hybridizes with Ce 4f band was lowered due to reduced O 2p repulsion arising from oxygen vacancies incurred by Y doping and therefore gave rise to the observed band-gap narrowing effect. Such switch-and-modulator scheme for band-gap engineering in nanocrystal materials can lead to important applications in environmental protection and solar energy harvesting technologies.

Dramatic band gap reduction incurred by dopant coordination rearrangement in Co-doped nanocrystals of CeO 2

A dramatic band gap narrowing of 1.61 eV has been observed in Co-doped nanocrystals of CeO2 (ceria), as a result of thermal annealing, without changing the ceria crystal structure and the Co concentration. As demonstrated by x-ray absorption fine structures, thermal annealing incurs an oxygen coordination rearrangement around Co atoms from an octahedral coordination to a square-planar coordination. First principle calculation using density functional theory reveals two stable oxygen coordination types surrounding Co, consistent with the experimental observation. The band gap values calculated for the two stable coordination types differ dramatically, reproducing the experimentally observed band gap narrowing. These prominent effects due to local structure rearrangement around dopant atoms can lead to unprecedented methods for band gap engineering in doped nanocrystal oxides.

Direct detection of fibrinogen in human plasma using electric-double-layer gated AlGaN/GaN high electron mobility transistors

Fibrinogen found in blood plasma is an important protein biomarker for potentially fatal diseases such as cardiovascular diseases. This study focuses on the development of an assay to detect plasmatic fibrinogen using electrical double layer gated AlGaN/GaN high electron mobility transistor biosensors without complex sample pre-treatment methods used in the traditional assays. The test results in buffer solution and clinical plasma samples show high sensitivity, specificity, and dynamic range. The sensor exhibits an ultra-low detection limit of 0.5 g/l and a detection range of 0.5–4.5 g/l in 1× PBS with 1% BSA. The concentration dependent sensor signal in human serum samples demonstrates the specificity to fibrinogen in a highly dense matrix of background proteins. The sensor does not require complicated automation, and quantitative results are obtained in 5 min with <5 μl sample volume. This sensing technique is ideal for speedy blood based diagnostics such as POC (point of care) tests, homecare tests, o...

Detection of C-reactive protein on an integrated microfluidic system by utilizing field-effect transistors and aptamers

Cardiovascular diseases (CVDs) cause more than 17 × 106 deaths worldwide on a yearly basis. Early diagnosis of CVDs is therefore of great need. The C-reactive protein (CRP) is an important biomarker for analyzing the risks of CVDs. In this work, CRP-specific aptamers with high sensitivity and specificity and field-effect-transistor (FET) devices were used to recognize and detect CRP by using an integrated microfluidic system automatically while consuming less volumes of reagents and samples (about 5 μm). In order to package the FET device into the microfluidic chip, a new method to prevent liquid leakage was proposed. Sensitive detection of CRP has been demonstrated on the developed microfluidic system. It is the first time that aptamer-FET assays could be realized on an integrated microfluidic system. Experimental results showed that the aptamer-FET assay was capable of detecting CRP with concentrations ranging from 0.625 mg/l to 10.000 mg/l, which may be promising for early diagnosis of CVDs.

Investigation of DNA Detection Mechanism with AlGaN/GaN High Electron Mobility Transistor (HEMT) Biosensor in High Ionic Strength Solution

In this research, the electrical double layer HEMT device is used to serve as the cardiovascular disease (CVD) RNA biomarkers biosensor. In this experiment, we try to use the DNA equivalent to miRNA-126 to test the ability of the novel DNA sensors. Short Debye length has been a haunted problem among all the field effect transistor (FET) biosensor for years. As the Debye length is extremely short in high ionic strength solutions, the traditional FET may not be directly detecting the biomolecule. The novel HEMT sensors using AlGaN/GaN can perform high sensitivity and great specificity in DNA sequences testing. The detection limit can be down to the 1fM and the specificity measurement can identify the signals between two DNA sequences with six-base mismatch. Furthermore, the mechanism of the sensor structure has also been studied. Since the structure of the device has the separation between source drain channel and gate electrode, the comparison with different electrode area and gap distance has been done as well. With repeating electrical measurement confirming, the reusability can also be seen after the 95℃ dehybridization process. With the Gibbs free energy ∆G of the specific sequences, we can also predict the equilibrium reaction constant and the binding ratio of probe DNA with the target DNA. The comparison between the thermal dynamics with the experiment consequence has been demonstrated too.