Ion-Selective Carbon Nanotube Field-Effect Transistors for Monitoring Drug Effects on Nicotinic Acetylcholine Receptor Activation in Live Cells.

We developed ion-selective field-effect transistor (FET) sensors with floating electrodes for the monitoring of the potassium ion release by the stimulation of nicotinic acetylcholine receptors (nAChRs) on PC12 cells. Here, ion-selective valinomycin-polyvinyl chloride (PVC) membranes were coated on the floating electrode-based carbon nanotube (CNT) FETs to build the sensors. The sensors could selectively measure potassium ions with a minimum detection limit of 1 nM. We utilized the sensor for the real-time monitoring of the potassium ion released from a live cell stimulated by nicotine. Notably, this method also allowed us to quantitatively monitor the cell responses by agonists and antagonists of nAChRs. These results suggest that our ion-selective CNT-FET sensor has potential uses in biological and medical researches such as the monitoring of ion-channel activity and the screening of drugs.

Semiconducting Carbon Nanotube-Based Nanodevices for Monitoring the Effects of Chlorphenamine on the Activities of Intracellular Ca2+ Stores.

We report a flexible and noninvasive method based on field-effect transistors hybridizing semiconducting single-walled carbon nanotubes for monitoring the effects of histamine on Ca2+ release from the intracellular stores of a nonexcitable cell. These nanodevices allowed us to evaluate the real-time electrophysiological activities of HeLa cells under the stimulation of histamine via the recording of the conductance changes of the devices. These changes resulted from the binding of histamine to its receptor type 1 on the HeLa cell membrane. Moreover, the effects of chlorphenamine, an antihistamine, on the electrophysiological activities of a single HeLa cell were also evaluated, indicating that the pretreatment of the cell with chlorpheniramine decreased intracellular Ca2+ release. Significantly, we only utilized a single nanodevice to perform the measurements for multiple cells pretreated with various concentrations of chlorphenamine. This enabled the statistically meaningful analysis of drug effects on cells without errors from device variations. Obtained results indicated the novel advantages of our method such as real-time monitoring and quantitative capability. Our devices, therefore, can be efficient tools for biomedical applications such as electrophysiology research and drug screening.

Micelle-stabilized Olfactory Receptors for a Bioelectronic Nose Detecting Butter Flavors in Real Fermented Alcoholic Beverages.

A bioelectronic nose device based on micelle-stabilized olfactory receptors is developed for the selective discrimination of a butter flavor substance in commercial fermented alcoholic beverages. In this work, we have successfully overexpressed ODR-10, a type of olfactory receptor, from Caenorhabditis elegans using a bacterial expression system at a low cost and high productivity. The highly-purified ODR-10 was stabilized in micelle structures, and it was immobilized on a carbon nanotube field-effect transistor to build a bioelectronic nose for the detection of diacetyl, a butter flavor substance, via the specific interaction between diacetyl and ODR-10. The bioelectronic nose device can sensitively detect diacetyl down to 10 fM, and selectively discriminate it from other substances. In addition, this sensor could directly evaluate diacetyl levels in a variety of real fermented alcoholic beverages such as beer, wine, and makgeolli (fermented Korean wine), while the sensor did not respond to soju (Korean style liquor without diacetyl). In this respect, our sensor should be a powerful tool for versatile food industrial applications such as the quality control of alcoholic beverages and foods.

Nafion-Radical Hybrid Films on Carbon Nanotube Transistors for Monitoring Antipsychotic Drug Effects on Stimulated Dopamine Release.

We developed floating electrode-based carbon nanotube biosensors for the monitoring of antipsychotic drug effects on the dopamine release from PC12 cells under potassium stimulation. Here, carbon nanotube field-effect transistors with floating electrodes were functionalized with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•) radicals by Nafion films. This method allows us to build selective biosensors for dopamine detection with a detection limit down to 10 nM even in the presence of other neurotransmitters such as glutamate and acetylcholine, resulting from the selective interaction between ABTS• radicals and dopamine. The sensors were also utilized to monitor the real-time release of dopamine from PC12 cells upon the stimulation of high-concentrated potassium solutions. Significantly, the antipsychotic effects of pimozide on the dopamine release from potassium-stimulated PC12 cells could also be evaluated in a concentration-dependent manner by using the sensors. The quantitative and real-time evaluation capability of our strategy should provide a versatile tool for many biomedical studies and applications.

Dye-functionalized Sol-gel Matrix on Carbon Nanotubes for Refreshable and Flexible Gas Sensors.

We report a colorimetric dye-functionalized sol-gel matrix on carbon nanotubes for use as a refreshable and flexible gas sensor with humidity calibration. Here, we fabricated gas sensors by functionalizing dye molecules on the top of carbon nanotube networks via a sol-gel method. Using hybrid gas sensors with different dye molecules, we could selectively detect various hazardous gases, such as NH3, Cl2 and SO2 gases, via optical and electrical signals. The sensors exhibited rather large conductance changes of more than 50% following exposure to gas species with concentrations even under the permissible exposure limit. Significantly, we could refresh used gas sensors by simply exposing them to fresh N2 gas without any heat treatment. Additionally, our sensors can be bent to form versatile practical sensor devices, such as tube-shape sensors for ventilation tubes. This work shows a simple but powerful method for building refreshable and selective gas sensors for versatile industrial and academic applications.

Modified Floating Electrode-Based Sensors for the Quantitative Monitoring of Drug Effects on Cytokine Levels Related with Inflammatory Bowel Diseases.

Modified floating electrode-based sensors were developed to quantitatively monitor the levels of tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine related with inflammatory bowel disease (IBD), and to evaluate the effect of drugs on the cytokine levels. Here, antibodies (anti-TNF-α) were immobilized on the floating electrodes of carbon nanotube devices, enabling selective and real-time detection of TNF-α among various cytokines linked to IBD. This sensor was able to measure the concentrations of TNF-α with a detection limit of 1 pg/L, allowing the quantitative estimation of TNF-α secretion from mouse macrophage Raw 264.7 cells stimulated by lipopolysaccharides (LPS). Notably, this method also allowed us to monitor the anti-inflammatory effect of a drug, lupeol, on the activation of the LPS-induced nuclear factor κB signaling in Raw 264.7 cells. These results indicate that our novel TNF sensor can be a versatile tool for biomedical research and clinical applications such as screening drug effects and monitoring inflammation levels.

Quantitative electrophysiological monitoring of anti-histamine drug effects on live cells via reusable sensor platforms.

We demonstrated the quantitative electrophysiological monitoring of histamine and anti-histamine drug effects on live cells via reusable sensor platforms based on carbon nanotube transistors. This method enabled us to monitor the real-time electrophysiological responses of a single HeLa cell to histamine with different concentrations. The measured electrophysiological responses were attributed to the activity of histamine type 1 receptors on a HeLa cell membrane by histamine. Furthermore, the effects of anti-histamine drugs such as cetirizine or chlorphenamine on the electrophysiological activities of HeLa cells were also evaluated quantitatively. Significantly, we utilized only a single device to monitor the responses of multiple HeLa cells to each drug, which allowed us to quantitatively analyze the antihistamine drug effects on live cells without errors from the device-to-device variation in device characteristics. Such quantitative evaluation capability of our method would promise versatile applications such as drug screening and nanoscale bio sensor researches.