Change In Channel Current Research Articles

Integrated microfluidic chip with a MIP-gated organic electrochemical transistor for continuous, selective, and label-free quantification of tumor marker

Early diagnosis of cancer is crucial to effective treatment of the patients and to higher survival rates. Tumor marker detection as an effective and noninvasive cancer diagnosis method has important clinical significance. N1, N12-diacetylspermine (DAS) is a new tumor marker. The development of its detection methods is an urgent need for medical diagnosis and human health monitoring. The conventional detection methods of DAS are labor-intensive and time-consuming approaches. In this work, a novel electrochemical detection platform was established by integrating an organic electrochemical transistor (OECT) with a microfluidic chip and applied for trace measurement of DAS. The sensing unit is a gate electrode in the OECT modified with molecularly imprinted polymers (MIPs), which can be used as an artificial receptor to realize label-free detection. The high specific recognition ability of MIPs films combined with the amplified function of an OECT yielded a highly sensitive and selective electrochemical detection chip. The integrated microfluidic channel controlledthe exact amount of solution to be delivered and provided real-time detection of DAS. The experimental results indicated that changes in channel current was proportional to DAS concentrations from 1 nM to 10 μM, with the detection limits of 0.8 nM. It is the first demonstration of the integration of a microfluidic system with a MIP-gated OECT for real-time tumor marker detection. The study results of this work helped to develop Point-Of-Care (POC) tools for the early diagnosis of lung cancer, colon cancer and breast cancer.

FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

The Gate-Modified Solution-Gated Graphene Transistors for the Highly Sensitive Detection of Lead Ions.

Lead ions are heavy metal ions that are extremely harmful to the human body and ecological environment. They can cause irreversible damage to the human nervous system and blood system at low concentrations. It is very important to develop a simple, rapid, and sensitive detection method of Pb2+. Solution-gated graphene transistors (SGGTs) have been widely studied in recent years due to their ultra-high sensitivity in chemical sensing. Herein, we have demonstrated a sensitive sensor of Pb2+ based on the SGGTs through the glutathione gate modification. When Pb2+ are added into the electrolyte solution, the electrical double layer capacitance near the gate electrode changes because Pb2+ can be strongly chelated, leading to the channel current change. The detection of Pb2+ can be realized. The detection limit of sensors for Pb2+ can reach 1 × 10-18 M, and the response time is about 1 s. The channel current change and the logarithm of Pb2+ concentration exhibit a good linear relationship in the concentration range of 1 × 10-18 and 1 × 10-6 M. Because the glutathione molecule can well recognize Pb2+, the devices also demonstrate good selectivity to Pb2+. Compared with the convention detection, our method shows easy operation, high sensitivity, and high selectivity. Therefore, it has great potential in the analysis of trace samples for health and environment monitoring.

Highly sensitive methyl parathion sensor based on Au-ZrO2 nanocomposites modified graphene electrochemical transistor

The excessive use of pesticides does great harm to environment and human health, a high performance sensor is urgently needed for the management of pesticides contamination. Herein, a novel graphene electrochemical transistor (GECT) for the detection of methyl parathion (MP) was successfully fabricated for the first time. A single layer of graphene was covered between the source and drain electrodes by the wet transfer method to act as channel for the transistor. Au-ZrO2 nanocomposites were electrodeposited at graphene channel of the device, considering the special affinity of ZrO2 nanoparticles toward phosphate group and electrocatalytic ability of Au nanoparticles. The sensing mechanism was attributed to the change of carrier concentration in channel induced by the electrochemical reaction of MP at the graphene channel, which built up the mathematic relationship between the change of channel current and the concentration of MP. Different modified materials and electrodeposition conditions were compared and optimized. Due to the high carrier mobility of graphene and excellent catalytic performance of Au-ZrO2 nanocomposites in the channel, the developed sensor showed a limit of detection as low as 0.1 ng/mL and ultra-wide linear range from 0.4 ng/mL to 7 μg/mL, which are comparable or superior to those using the large-scale instruments. Meanwhile, the device exhibited good selectivity toward usual interferents and high accuracy for detection of MP in Chinese cabbage samples, demonstrating the promising practicality of the devices. It is expected that GECT can act as a desirable transducer platform for highly sensitive and selective detection of pesticides.

Involvement of p75NTR in the effects of Aβ on L-type Ca2+ channel in cultured neuronal networks

Ca2+ overload in neurons has been implicated in Alzheimer's Disease (AD). Upregulation of Ca2+ through L-type Ca2+ channels was known to be involved in the neurodegeneration induced by amyloid-β (Aβ) peptides in AD. However, little is known about the mechanism by which upregulation of L-type Ca2+ channel currents is linked to Aβ-induced neuronal toxicity. In the present study, we found that the L-type Ca2+ current in transgenic AD mice (Tg2576) neurons is greater than in wild-type (WT) neurons, and this Ca2+ channel current change were rescued in Tg2576/p75NTR+/− (p75 neurotrophin receptor) neurons. We further examined the changes in the gating of L-type Ca2+ channels following Aβ42 treatment, and the results showed that the L-type Ca2+ channel current was significantly increased by Aβ42 treatment in WT hippocampal neurons. Blocking or decreasing the expression of p75NTR eliminated the influence of Aβ42 on the L-type Ca2+ channel current in WT hippocampal neurons. We also evaluated how Aβ42 affected the voltage-dependent activation and inactivation of L-type Ca2+ channels in cultured WT neurons. The results indicated that the half-maximal activation voltage (V1/2) was left shifted, and the half-inactivation voltage (V1/2) displayed a right shift in neuron treated by Aβ42. Decreasing the expression of p75NTR eliminated the effect of Aβ42 on voltage-dependent activation and inactivation of the L-type Ca2+ channel. These results indicate that Aβ42 changes L-type Ca2+ channel currents by modulating the channel's activation and inactivation dynamics, while decreasing p75NTR expression can remove this effect.

Functional Carbon Quantum Dots for Highly Sensitive Graphene Transistors for Cu2+ Ion Detection.

Cu2+ions play essential roles in various biological eventsthat occur in the human body. It is important to establish an efficient and reliable detection of Cu2+ ions for people's health. The solution-gated graphene transistors (SGGTs) have been extensively investigated as a promising platform for chemical and biological sensing applications. Herein, highly sensitive and highly selective sensor for Cu2+ ion detection is successfully constructed based on SGGTs with gate electrodes modified by functional carbon quantum dots (CQDs). The sensing mechanism of the sensor is that the coordination of CQDs and Cu2+ ions induces the capacitance change of the electrical double layer (EDL) near the gate electrode and then results in the change of channel current. Compared to other metal ions, Cu2+ ions have an excellent binding nature with CQDs that make it an ultrahigh selective sensor. The CQD-modified sensor achieves excellent Cu2+ ion detection with a minimal level of concentration (1 × 10-14 M), which is several orders of magnitude lower than the values obtained from other conventional detection methods. Interestingly, the device also displays a quick response time on the order of seconds. Due to the functionalized nature of CQDs, SGGTs with CQD-modified gate show good prospects to achieve multifunctional sensing platform in biochemical detections.

Mechanism of AlGaAs/InGaAs pHEMT Nonlinear Response Under High-Power Microwave Radiation

With the development of microelectronic technology, the reliability of devices in a complex electromagnetic environment has become one of the greatest challenges in the semiconductor industry. On this basis, a phenomenon of nonlinear transient response is observed in high-power microwave (HPM)-radiating AlGaAs/InGaAs pseudomorphic high-electron-mobility transistors (pHEMTs). This abnormal response is induced before the thermal failure, causing disturbances to the circuit. To understand this phenomenon, a detailed mechanism analysis is proposed. The analysis shows that the nonlinear response is initially associated with the 2DEG velocity saturation, then a breakdown process is induced by the tunneling and impact ionization combined effect. Within each radiation period, the channel current changes its direction twice under the influence of the HPM field. The nonlinear response current $I_{d}$ is derived from the theoretical analysis. TCAD simulations demonstrate the saturation and breakdown process. Corresponding experiments are performed using a Ka-band low-noise amplifier (LNA) chip. The results support the theory well.

Selective recognition of Histidine enantiomers using novel molecularly imprinted organic transistor sensor

Abstract l -Histidine (L-His) is an essential bioactive amino acid, playing a significant role in several biological processes. Therefore, the accurate determination of L-His is of great significance to human health. In this work, a strategy was developed for the chiral detection of L-His using an organic electrochemical transistor (OECT) sensor based on molecularly imprinted polymer (MIP). MIP films were electrodeposited on OECT gate platforms. MIP films designed for specifically recognizing His combined with the amplified function of an OECT yielded highly sensitive and selective OECT biosensor. The properties of the resulting biosensor were characterized by various analytical methods. The results indicated that changes in channel current was proportional to D-His and L-His concentrations from 100 nM to 10 μM, with the detection limits of 10 nM and 100 nM (S/N > 3), respectively. Furthermore, the highly selective MIP film allowed to differentiate L-His from D-His or D-His from L-His. In terms of selectivity, the tests suggested apparent differences in channel current changes between L-His and D-His and interferences. The applicability of the biosensor for L-His detection in human urine demonstrated this sensor will be ideal transducers for disposable applications in the future.

Highly selective and sensitive sensor based on an organic electrochemical transistor for the detection of ascorbic acid

In this study, an organic electrochemical transistor sensor (OECT) with a molecularly imprinted polymer (MIP)-modified gate electrode was prepared for the detection of ascorbic acid (AA). The combination of the amplification function of an OECT and the selective specificity of MIPs afforded a highly sensitive, selective OECT sensor. Cyclic voltammetry and electrochemical impedance spectroscopy measurements were carried out to monitor the stepwise fabrication of the modified electrodes and the adsorption capacity of the MIP/Au electrodes. Atomic force microscopy was employed for examining the surface morphology of the electrodes. Important detection parameters, pH and detection temperature were optimized. With the change in the relative concentration of AA from 1μM to 100μM, the MIP-OECT sensor exhibited a low detection limit of 10nM (S/N > 3) and a sensitivity of 75.3μA channel current change per decade under optimal conditions. In addition, the MIP-OECT sensor exhibited excellent specific recognition ability to AA, which prevented the interference from other structurally similar compounds (e.g., aspartic acid, glucose, uric acid, glycine, glutathione, H2O2), and common metal ions (K+, Na+, Ca2+, Mg2+, and Fe2+). In addition, a series of vitamin C beverages were analyzed to demonstrate the feasibility of the MIP-OECT sensor. Using the proposed principle, several other sensors with improved performance can be constructed via the modification of organic electrochemical transistors with appropriate MIP films.

A Novel Organic Electrochemical Transistor-Based Platform for Monitoring the Senescent Green Vegetative Phase of Haematococcus pluvialis Cells.

The freshwater unicellular microalga Haematococcus pluvialis (H. pluvialis) has gained increasing attention because of its high-value metabolite astaxanthin, a super anti-oxidant. For the maximum astaxanthin production, a key problem is how to determine the senescent green vegetative phase of H. pluvialis cells to apply the astaxanthin production inducers. The conventional methods are time-consuming and laborious. In this study, a novel platform based on organic electrochemical transistor (OECT) was produced. A significant channel current change of OECTs caused by settled H. pluvialis cells on the poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT: PSS) film was recorded commencing from 75 min and a stationary stage was achieved at 120 min after the combined treatment of blue light irradiation and sodium bicarbonate solution additives, which indicate the onset and maturation of the senescent green vegetative phase, respectively. Therefore, the appropriate time point (120 min after sample loading) to apply astaxanthin production inducers was determined by as-fabricated OECTs. This work may assist to develop a real-time biosensor to indicate the appropriate time to apply inducers for a maximum astaxanthin production of H. pluvialis cells.

Nonvolatile MoS2 field effect transistors directly gated by single crystalline epitaxial ferroelectric

We demonstrate non-volatile, n-type, back-gated, MoS2 transistors, placed directly on an epitaxial grown, single crystalline, PbZr0.2Ti0.8O3 (PZT) ferroelectric. The transistors show decent ON current (19 μA/μm), high on-off ratio (107), and a subthreshold swing of (SS ∼ 92 mV/dec) with a 100 nm thick PZT layer as the back gate oxide. Importantly, the ferroelectric polarization can directly control the channel charge, showing a clear anti-clockwise hysteresis. We have self-consistently confirmed the switching of the ferroelectric and corresponding change in channel current from a direct time-dependent measurement. Our results demonstrate that it is possible to obtain transistor operation directly on polar surfaces, and therefore, it should be possible to integrate 2D electronics with single crystalline functional oxides.

Kv1.3 channel current changes in neutrophilic asthma and eosinophilic asthma

Objective Allergic asthma is a chronic inflammatory disease of the airways.T lymphocytes play important roles in the pathogenesis of asthma.The voltage-gated Kv1.3 potassium channel may be a key factor in the activation of T lymphocytes.This research aims to detect the function of Kv1.3 channel in the neutrophlial asthma(NA)model and eosinophilic asthma(EA)model. Methods A total of 24 mice were randomly assigned into three groups: control, neutrophilic asthma model and eosinophilic asthma group.Neutrophilic asthma model was established with ovalbumin(OVA)and lipopolysaccharide(LPS); eosinophilic asthma was established with OVA and Al(OH)3; airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument; lung inflammation changes were observed by pathological HE staining; IL-17A and IL-4 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA; Kv1.3 channel protein level in lung was evaluated by western blot; the change of current density in CD4+ .T lymphocytes were tested by whole-cell patch clamp technique. Results Levels of IL-17A and IL-4 in bronchoalveolar lavage fluid increased in both NA and EA model(P<0.05). Compare with EA model, the IL-17A level was significantly higer in NA model, while the IL-4 level was significantly lower.In NA and EA model, kv1.3 protein expression in lung tissue was significantly higher than that in the control group(P<0.05), and kv1.3 protein expression in NA model was significantly higer than that in the EA model(P<0.05). Current intensity and current density of kv1.3 channel increased in both NA and EA model.While the current intensity and current density of kv1.3 channel were significantly higher in NA model than that in EA model. Conclusion Kv1.3 protein level, Kv1.3 channel current intensity and kv1.3 channel current density increased in both NA and EA model, especially in NA group, providing a new way for treatment of bronchial asthma. Key words: Neutrophlial asthma; Eosinophilic Asthma; Kv1.3 channel

Electrical Detection of Trapped Charge Displacements Using an Ultra-Thin SOI Percolation Transistor

Electrical detection of solid-state charge qubits requires ultra-sensitive charge measurement, typically using a quantum point contact or single-electron-transistor, which imposes strict limits on operating temperature, voltage and current. A conventional FET offers relaxed operating conditions, but the back-action of the channel charge is a problem for such small quantum systems. Here, we discuss the use of a percolation transistor as a measurement device, with regard to charge sensing and backaction. The transistor is based on a 10nm thick SOI channel layer and is designed to measure the displacement of trapped charges in a nearby dielectric. At cryogenic temperatures, the trapped charges result in strong disorder in the channel layer, so that current is constrained to a percolation pathway in sub-threshold conditions. A microwave driven spatial Rabi oscillation of the trapped charge causes a change in the percolation pathway, which results in a measurable change in channel current.

Electrical characterization of single cells using polysilicon wire ion sensor in an isolation window

A polysilicon wire (PSW) sensor can detect the H(+) ion density (pH value) of the medium coated on its surface, and different cells produce different extracellular acidification and hence different H(+) ion densities. Based on this, we used a PSW sensor in combination with a mold-cast polydimethylsiloxane (PDMS) isolation window to detect the adhesion, apoptosis and extracellular acidification of single normal cells and single cancer cells. Single living human normal cells WI38, MRC5, and BEAS-2B as well as non-small-cell lung cancer (NSCLC) cells A549, H1299, and CH27 were cultivated separately inside the isolation window. The current flowing through the PSW channel was measured. From the PSW channel current change as a function of time, we determined the cell adhesion time by observing the time required for the current change to saturate, since a stable extracellular ion density was established after the cells were completely adhered to the PSW surface. The apoptosis of cells can also be determined when the channel current change drops to zero. We found that all the NSCLC cells had a higher channel current change and hence a lower pH value than the normal cells anytime after they were seeded. The corresponding average pH values were 5.86 for A549, 6.00 for H1299, 6.20 for CH27, 6.90 for BEAS-2B, 6.96for MRC5, and 7.02 for WI38, respectively, after the cells were completely adhered to the PSW surface. Our results show that NSCLC cells have a stronger cell-substrate adhesion and a higher extracellular acidification rate than normal cells.

Single channel properties of lysenin measured in artificial lipid bilayers and their applications to biomolecule detection

Single channel currents of lysenin were measured using artificial lipid bilayers formed on a glass micropipette tip. The single channel conductance for KCl, NaCl, CaCl2, and Trimethylammonium-Cl were 474 ± 87, 537 ± 66, 210 ± 14, and 274 ± 10 pS, respectively, while the permeability ratio PNa/PCl was 5.8. By adding poly(deoxy adenine) or poly(L-lysine) to one side of the bilayer, channel currents were influenced when membrane voltages were applied to pass the charged molecules through the channel pores. Current inhibition process was concentration-dependent with applied DNA. As the current fluctuations of α-hemolysin channels is often cited as the detector in a molecular sensor, these results suggest that by monitoring channel current changes, the lysenin channel has possibilities to detect interactions between it and certain biomolecules by its current fluctuations.

High‐speed video observations of rocket‐and‐wire initiated lightning

We present observations of a rocket‐and‐wire triggered lightning flash obtained with high‐speed video cameras recording 5400 and 50000 frames per second (frame times 185 μs and 20 μs) with time‐synchronized current and electric field measurements. Transient leader channels were observed with precursor current pulses occurring before the development of the sustained upward positive leader that initiated the initial continuous current. The sustained upward positive leader stepped with a constant speed of 5.6 × 104 m s−1 over its initial 100 m. The wire destruction occurred discontinuously over a time of 7 ms about 45 ms after sustained upward leader inception, with a small change in channel current. Downward leaders, upward connecting leaders, and filamentary streamers were imaged in the bottom 50 m of the channel. We present the first images of a negative step forming in lightning, apparently involving a space stem similar to steps in meter‐length negative laboratory sparks.

A Laterally Movable Gate Field Effect Transistor

A laterally movable gate field effect transistor (LMGFET) device that directly couples lateral mechanical gate motion to drain current of a FET is presented in this paper. Lateral motion of the FET gate results in a change in channel width, keeping the channel length and the gap between the gate and the oxide layer constant. This results in a change in channel current that, in principle, is linearly proportional to mechanical motion. The operating principle of an LMGFET, along with details of the fabrication process for a depletion-type LMGFET device, is described. Fabricated LMGFET shows an average drain current sensitivity to gate motion of -5.8 ¿A/¿m at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> = 20 V and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GS</sub> = 0 V for 60-¿m gate motion. A model for the fabricated LMGFET is developed based on electrical measurements. The device shows promise both as a sensor and as an actuator in MEMS and other related applications.

Sensors Based on Organic Thin Film Transistors

Organic thin-film transistors (OTFT) are excellent candidates for the application on disposable sensors due to their potentially low-cost and easy fabrication process. Two types of OTFT-based sensors have been studied. One is light sensitive phototransistor based on the composite of poly(3-hexylthiophene) and TiO2 nanoparticles. The device shows a quick change of channel current under light exposure, which can be attributed to a positive shift of the threshold voltage induced by accumulated electrons trapped by the TiO2 nanoparticles in the channel. Another one is for sensing DNA hybridization. Both single and double strand DNA molecules are immobilized on the surface of the Au source/drain electrodes of different devices, inducing a dramatic change in the performance of the OTFTs. Single strand DNA and double strand DNA are differentiated successfully in the experiments indicating that this is a promising technique for sensing DNA hybridization without labeling.

Organic phototransistor based on poly(3-hexylthiophene)/TiO2 nanoparticle composite

Light sensitive phototransistor based on the composite of poly(3-hexylthiophene) and TiO2 nanoparticles has been developed. The device shows a quick change in channel current under light exposure, which can be attributed to a positive shift of the threshold voltage, while no change in the field effect mobility and off current can be observed. The shift of the threshold voltage is induced by accumulated electrons trapped by the TiO2 nanoparticles in the channel. The photosensitivity of the device has been found to be dependent on the concentration of TiO2 nanoparticles, the incident wavelength and the voltage between the source and drain.

Functional Coupling between the Kv1.1 Channel and Aldoketoreductase Kvβ1

The Shaker family voltage-dependent potassium channels (Kv1) assemble with cytosolic beta-subunits (Kvbeta) to form a stable complex. All Kvbeta subunits have a conserved core domain, which in one of them (Kvbeta2) is an aldoketoreductase that utilizes NADPH as a cofactor. In addition to this core, Kvbeta1 has an N terminus that closes the channel by the N-type inactivation mechanism. Point mutations in the putative catalytic site of Kvbeta1 alter the on-rate of inactivation. Whether the core of Kvbeta1 functions as an enzyme and whether its enzymatic activity affects N-type inactivation had not been explored. Here, we show that Kvbeta1 is a functional aldoketoreductase and that oxidation of the Kvbeta1-bound cofactor, either enzymatically by a substrate or non-enzymatically by hydrogen peroxide or NADP(+), induces a large increase in open channel current. The modulation is not affected by deletion of the distal C terminus of the channel, which has been suggested in structural studies to interact with Kvbeta. The rate of increase in current, which reflects NADPH oxidation, is approximately 2-fold faster at 0-mV membrane potential than at -100 mV. Thus, cofactor oxidation by Kvbeta1 is regulated by membrane potential, presumably via voltage-dependent structural changes in Kv1.1 channels.