ZnO nanorods array based field-effect transistor biosensor for phosphate detection

Viral infections are one of the main causes of deaths and economic losses around the globe, and effective virus detection methods are essential for epidemic prevention and control. Most existing detection methods have problems such as high false negative/positive rates, slow responses, high costs, and dependence on professional equipment and personnel, which are not conducive to the rapid and accurate detection of viruses. Field effect transistor (FET) biosensors have attracted widespread attention due to their advantages of label-free detection, high sensitivity, fast responses, real-time measurement, low power consumption, and small sizes for portability. This article first briefly describes the basic situation of viruses and the structure and detection principle of FET biosensors. Subsequently, it delves into the research achievements in the application of FET biosensors in the detection of influenza viruses, hepatitis viruses, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2. Finally, we make a comprehensive summary and reasonable outlook on the role played by FET biosensors in biomedicine.

Ever-growing tissue regeneration and other stem cell therapies cause pressing need for large population of self-renewable stem cells. However, stem cells gradually lose their stemness after long-term in vitro cultivation. In this study, a ZnO nanorod (ZnO NR) array is used to maintain the stemness of human adipose-derived stem cells (hADSCs). The results prove that after culturing hADSCs on ZnO NRs for 3 weeks, the stemness genes and protein expression level are higher than that on culture plates and ZnO film. ZnO NRs can maintain stemness of hADSCs without inhibiting the cell proliferation and oriented differentiation capabilities. KLF4 (Kruppel-like factor 4) is a Zn2+ -binding gene that plays a vital role in cell proliferation and differentiation. Sustained Zn2+ release and the increased expression of KLF4 can be detected, suggesting that ZnO NRs have efficiently released Zn2+ for stemness maintenance. Taken together, the nanotopography of ZnO NRs and the Zn2+ release synergistically facilitate stemness maintenance. This study has provided a powerful tool for directing cell fate, maintaining stemness, and realizing the expansion of stem cells in vitro, which will open a new route for the manufacture of large populations of stem cells and fulfilling the growing demand for the cell therapy market.

The dosage of 5-fluorouracil (5-FU), which is a widely used for cancer medication, is determined based on body surface area, although efficacy largely depends on the liver function of the individual, resulting that only 21% patients are given an optimal dose of 5-FU in these years. The measurement of the 5-FU concentration in the blood enables us to adjust individual dose adjustment. Conventional methods for 5-FU detection such as an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography are not very suitable for clinical applications because they need time-consuming procedure with expensive equipments. Detection of 5-FU using a field effect transistor (FET) biosensor, which enables rapid and simple measurement, is expected to solve such problems. However, FET biosensor, which detects changes in its surface density due to the adsorption of charged molecules, was unable to detect uncharged 5-FU. In this study, a method for the FET biosensing to detect 5-FU exploiting sequential adsorption of 5-FU modified bovine serum albumin (BSA/5-FU) was proposed. By using this method, FET responses caused by the adsorption of negatively charged BSA/5-FU depending on the 5-FU concentration were detected. The SiO2 surface of the FET gate insulator was exposed to O2 plasma to introduce hydroxyl groups. After the exposure, the surface was exposed to 3-aminopropyltriethoixysilane (APTES), followed by the modification of the cross-linker, glutaraldehyde (GA). A single chain variable fragments (ScFv) and antigen binding fragments (Fab) were allowed to react with each activated GA-modified FET. After the immobilization, the residual aldehyde-groups were treated by ethanolamine to suppress the non-specific adsorption. V g-I d characteristics were measured before and after dripping of both 5-FU and BSA/5-FU on the ScFv- and Fab-immobilized FET biosensors. Finally, threshold voltage shifts (∆V g) caused by the adsorption of BSA/5-FU were obtained. To compare the capture capability of ScFv and Fab, the electrical responses of the FET biosensors functionalized with the two receptors due to the adsorption of BSA/5-FU were measured. The responses of ScFv- and Fab-immobilized FET biosensor caused by dripping of 25 μg/mL BSA/5-FU were +25 mV and +40 mV, respectively. The difference between ΔV g values for these two FET sensors using ScFv or Fab can be ascribed to the difference of affinity [1]. To verify the specificity of Fab-immobilized FET biosensor, ∆V g was measured when human serum albumin (HSA) was dropped on the FET biosensor, and the ∆V g was hardly observed. Additionally, the atomic force microscopic (AFM) images on the FET gate surface shows that the size of observed particles matches the size of BSA/5-FU, while the surface morphology and roughness are not significantly changed. These results indicated that Fab-immobilized surface specifically captured BSA/5-FU. To investigate the quantitative detectability of the Fab-immobilized FET biosensor, we measured the FET responses corresponding to the amount of adsorbed BSA/5-FU, which was related with the concentrations of 5-FU. As a result, the magnitude of ∆V g by dripping of 1000 ng/mL 5-FU and 25 μg/mL BSA/5-FU was reduced to +12 mV compared with the response of 25 µg/mL BSA/5-FU (Figure 1). These results can be attributed to that the adsorbed 5-FU inhibited the adsorption of BSA/5-FU to the Fab-immobilized surface. Therefore, we conclude that the detection of 5-FU using the FET biosensors by applying the charged BSA/5-FU is a promising simple method for monitoring the concentration of 5-FU.Reference:[1] Y. Reiter, et al., J. Biol. Chem., 269, 28, 18327-18331 (1994).Figure 1 V g-I d characteristics of Fab-immobilized FET biosensor before and after dripping of (a) 0 ng/mL 5-FU and 25 µg/mL BSA/5-FU or (b) 1000 ng/mL 5-FU and 25 µg/mL BSA/5-FU. Figure 1

Field effect transistor (FET) biosensor was considered as a valuable tool for detection of chemical and biological molecules over the past decades [1]. The basic principle of FET biosensor is by converting the variation in the surface potential of gate insulator into the conductivity change in the semiconductor channel. Such kind of direct detection can interestingly offers a simple, label-free and reliable sensing mechanism. However, to configure highly sensitive sensor, the FET signal is strongly depend on the electric field resulting from the binding of charged molecule to the gate surface. Hence, the charge of target molecule is a key factor for electrically-based sensing in which the FET biosensor in some cases hampers to be applied for the detection of low charge density of molecules and neutral molecules. In this research, we designed two approaches of charge amplification including (i) addition of metal ions as second ligand, and (ii) chemical modification via coupling reaction as illustrated at Figure 1. These strategies were performed into the target protein that can increase the charge of proteins, leading to the enhancement of FET signal. Here, we used and detected prion proteins as a model of the target protein. Highly sensitive method for detecting prion proteins is a top priority for early diagnosis and minimizing the spread of the diseases [2], and the amplified FET signal is of utmost importance to meet the goal for improving the sensitivity of prion detection to the lowest concentration as possible. Firstly, by utilizing thiamine as probe molecule, the surface of FET biosensor can specifically interact with the prion protein as confirmed by FET response, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) analysis [3]. Then, the sensitivity of thiamine-immobilized FET to the prion protein in human serum sample before the use of amplification step was quantitatively determined and achieved at the concentration of 400 pM, which is also lower than the cut-off value (2 nM). Furthermore, the amplification process was applied. As for approach (i), by taking the advantage of specific interaction between prion protein and copper (II) ions (Cu2+), a model of dual-ligand binding consist of thiamine immobilized surface, prion protein and Cu2+was performed and successfully generated an enhancement of FET response. As for approach (ii), we demonstrated the feasibility of protein modification with conventional coupling reaction, converting the carboxylate group (anionic) to the amino group (cationic) of prion protein. These strategies can result higher electrical signals in prion detection based on FET biosensor. The detail of experimental procedure and mechanism will be discussed further in the conference. In summary, the FET biosensor device could provide a promising technique and a pave way for highly sensitive detection of prion protein.

<p>The efficient detection of disease-relevant biomolecules in untreated clinical samples is highly desired, especially for acute diseases. Field-effect transistor (FET) biosensors allow label-free and rapid detection of biomolecules through the measurement of their intrinsic charges. However, the sensitivity of FET biosensors would be undermined by the charge screening effect in practical biological media with high ionic strength. Here, we report the design and performance of a nanostructured interface-engineered field effect transistor (NIE FET) biosensor for highly sensitive detection of cardiovascular disease (CVD)-associated miRNAs in serum samples. Molecular dynamic simulations and electrochemical characterizations demonstrate that the nanostructured interface with concave regions alleviates the charge screening effect and enlarges the Debye length. The rationally designed NIE FET biosensor exhibits high sensitivity and reproducibility in detecting miRNA in untreated serum samples with a detection limit of pM level. Benefiting from its excellent detection capabilities, NIE FET reveals the relationship between miRNAs and CVDs and realizes the effective classification of different CVD types with the help of machine learning algorithms. The construction of NIE FET defines a robust strategy for electrical biomolecular detection in practical clinical samples.</p>

Density-controlled zinc oxide (ZnO) nanorod arrays were synthesized on indium tin oxide (ITO) substrates via a potentiostatic electrodeposition method under different conditions. The effects of preparing conditions on the density of nanorods were systematically investigated by scanning electron microscopy (SEM) and X-ray diffraction (XRD). It is demonstrated that the density and diameter of ZnO nanorods can be effectively controlled by varying the electrodeposition parameters, such as electrodeposition potential, concentration of Zn2+ precursor and growth temperature. Pre-treatment of the substrate also has great influence on the morphology of the electrodeposited ZnO nanorods. By coating the ITO substrates with an gold (Au) or ZnO nanoparticle seed layer, ZnO nanorod arrays with an average diameter of about 50 nm were synthesized, and the nanorod density can be controlled to above 50 x 10(8) rod cm(-2), which is several dozen times greater than that of the ZnO nanorod arrays synthesized on original ITO substrates.

Proteins have been one of the most important biomarkers for diagnosing diseases, and field-effect transistor (FET) biosensors possess high sensitivity; are label-free; and feature real-time detection, rapidity, and easy integration for protein detection. FET biosensors are mainly made up of FET parts, such as channel materials, and bio parts, such as receptors. This Tutorial provides an in-depth exploration of FET biosensors for protein detection from the composition perspective and discusses the commercialization of point-of-care diagnostics of proteins based on FET biosensors.

Effect of diameter and height of electrochemically-deposited ZnO nanorod arrays on the performance of piezoelectric nanogenerators

Signal amplification in electrochemical detection of buckwheat allergenic protein using field effect transistor biosensor by introduction of anionic surfactant

Effect of heat and time-period on the growth of ZnO nanorods by sol–gel technique

The highly sensitive and cost-free field effect transistor (FET) biosensor for specific detection of DNA and streptavidin based on Zinc Oxide Nanowires (NWs) to develop the next generation biosensors in label-free approach under electrochemical gate modulation has been materialized. The electronic properties of NWs were changed by binding of charged analytes to NWs surface under electrochemical gate modulation. Due to highly chemically inertness, immobilization of the target analyte receptors on the NWs could be conducted through electrochemical treatment. For materialization of DNA binding, gold nanoparticles (Au NPs) were used to functionalize ZnO NWs surface. In this work, a liquid gated FET based on NWs was configured to detect the complementary DNA strand hybridization as well as the protein streptavidin at very low concentration. The biosensor could reach to sensitivity of attomolar. The sensitivity of response was check and biosensor showed the sensitivity ranges from 10−18 to 10−12 mol.L−1. The FET biosensor could distinguish a complementary strand from a single nucleotide polymorphism (SNP) containing strand. The limit of detection (LOD) reached to15 aM. The NPs decoration on the NWs surface brought about the high detection limit. The NPs decoration was being a promising method and scientific approach for biomolecules detection.

Sensitive electrical detection of human prion proteins using field effect transistor biosensor with dual-ligand binding amplification.

A high sensitivity field effect transistor biosensor for methylene blue detection utilize graphene oxide nanoribbon

Highly oriented Ga-doped zinc oxide (ZnO) nanorod arrays have been prepared on aZnO-buffered silicon substrate in an aqueous solution, which is a mixture of methenamine(C6H12N4), zinc nitratehexahydrate (Zn(NO3)2·6H2O), andgallium nitrate hydrate (Ga(NO3)3·xH2O). The microstructure characteristics and optical properties of the nanorod arrays wereanalyzed using different characterization techniques including field-emission scanningelectron microscopy (FESEM), x-ray photoelectron spectroscopy (XPS), andphotoluminescence (PL). The experimental results show that the morphology,density, and surface compositions of ZnO nanorod arrays are sensitive to theconcentration of gallium nitrate hydrate. The PL spectra of all ZnO nanorodarrays show three different emissions, including UV (ultraviolet), yellow, andNIR (near infrared) emissions. With the increase in the Ga doping level, theluminescence quality of ZnO nanorods has been improved. The peak of UV emissionhas a small redshift, which can be ascribed to the combined effect of size andGa doping. Furthermore, Ga doping has caused defects that respond to NIRemission.

Field-effect transistor (FET) biosensors based on two-dimensional (2D) materials have drawn significant attention due to their outstanding sensitivity. However, the Boltzmann distribution of electrons imposes a physical limit on the subthreshold swing (SS), and a 2D-material biosensor with sub-60 mV/dec SS has not been realized, which hinders further increase of the sensitivity of 2D-material FET biosensors. Here, we report tunnel FETs (TFETs) based on a SnSe2/WSe2 heterostructure and observe the tunneling effect of a 2D material in aqueous solution for the first time with an ultralow SS of 29 mV/dec. A bilayer dielectric (Al2O3/HfO2) and graphene contacts, which significantly reduce the leakage current in solution and contact resistance, respectively, are crucial to the realization of the tunneling effect in solution. Then, we propose a novel biosensing method by using tunneling current as the sensing signal. The TFETs show an extremely high pH sensitivity of 895/pH due to ultralow SS, surpassing the sensitivity of FET biosensors based on a single 2D material (WSe2) by 8-fold. Specific detection of glucose is realized, and the biosensors show a superb sensitivity (3158 A/A for 5 mM), wide sensing range (from 10-9 to 10-3 M), low detection limit (10-9 M), and rapid response rate (11 s). The sensors also exhibit the ability of monitoring glucose in complex biofluid (sweat). This work provides a platform for ultrasensitive biosensing. The discovery of the tunneling effect of 2D materials in aqueous solution may stimulate further fundamental research and potential applications.