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Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion-and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated.ionic transistor | ionic transport | conducting polymers | cell signaling N umerous biochemical, biomedical and clinical applications demand technology allowing for the spatiotemporally controlled delivery of ions and biomolecules. In order to gain dynamic control of cellular microenvironments, substance delivery in complex high-resolution patterns where each point of delivery is individually addressable is required. In analogy to the addressing schemes found in active matrix displays (1, 2), addressability in active chemical circuits can be achieved by introducing transistor functionality into each delivery point. Transistors are generally three-terminal devices in which the current between the first and second terminals is controlled by an electric signal applied to the third. The semiconductor solid-state transistor (3) is the key component that enables amplification, addressing, and processing of electronic signals in circuits. Analogously, a transistor based on transport of ions rather than electrons would render the same functionality possible in chemical circuits, e.g., for addressable delivery of charged ions and biomolecules. To date, few reports of transistor-like active control of ion transport have been published (4-8). The principle of operation in the majority of these devices is the modulation of the surface charge in nanochannels and nanoporous membranes. However, these devices are typically difficult to manufacture, hard to integrate into circuits, and do not operate well at the high ion concentrations required to generate physiologically relevant conditions. Bipolar junction transistors (BJTs) (3) are a major class of transistors with their own nomenclature: The input, output, and control terminals are denoted emitter, collector, and base, respectively. A pnp-BJT can bee seen as two pn-junctions sharing a narrow base region, where the emitter and collector are p-doped and the base is n-doped. Anion-and cation-selective membranes (9) are the ionic equivalents to n-and p-doped semiconductors, respectively. These membranes contain fixed ionic groups compensated by mobile ions of the opposite charge (counterions). Mobile ions of t...

A miniaturized organic electronic ion pump (OEIP) based on conjugated polymers is developed for delivery of positively charged biomolecules. Characterization shows that applied voltage can precisely modulate the delivery rate of the neurotransmitter acetylcholine. The capability of the device is demonstrated by convection‐free, spatiotemporally resolved delivery of acetylcholine via a 10 µm channel for dynamic stimulation of single neuronal cells.

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Background There is a high prevalence of dental anxiety in children and adolescents. Cognitive behavioral therapy is emerging as a treatment option. Aim The purpose of this study is to explore how children with dental anxiety and their parents experience cognitive behavioral therapy (CBT) in dentistry. Design We interviewed 12 children and one of their parents and conducted a thematic analysis of the transcribed interviews. Results Perspective shift emerged as overarching theme in our thematic analysis. This theme consisted of three main themes, which were mastery, safety, and reduced fear. Six subthemes were also identified according to our analyses. Mastery includes two subthemes, gradual exposure and autonomy and control. Subthemes and sources for safety feeling were therapeutic alliance and changed appraisal. The theme reduced fear also consisted of two subthemes; reduced anticipatory anxiety and coping. Conclusions The results show that parents and children had positive experiences of CBT and its outcome and were able to benefit from this psychological treatment when dealing with dental anxiety.

A central circadian (~24 hr) clock coordinating daily rhythms in physiology and behavior resides in the suprachiasmatic nucleus (SCN) located in the anterior hypothalamus. The clock is directly synchronized by light via the retina and optic nerve. Circadian oscillations are generated by interacting negative feedback loops of a number of so called "clock genes" and their protein products, including the Period (Per) genes. The core clock is also dependent on membrane depolarization, calcium and cAMP 1 . The SCN shows daily oscillations in clock gene expression, metabolic activity and spontaneous electrical activity. Remarkably, this endogenous cyclic activity persists in adult tissue slices of the SCN [2][3][4] . In this way, the biological clock can easily be studied in vitro, allowing molecular, electrophysiological and metabolic investigations of the pacemaker function.The SCN is a small, well-defined bilateral structure located right above the optic chiasm 5 . In the rat it contains ~8.000 neurons in each nucleus and has dimensions of approximately 947 μm (length, rostrocaudal axis) x 424 μm (width) x 390 μm (height) 6 . To dissect out the SCN it is necessary to cut a brain slice at the specific level of the brain where the SCN can be identified. Here, we describe the dissecting and slicing procedure of the SCN, which is similar for mouse and rat brains. Further, we show how to culture the dissected tissue organotypically on a membrane 7 , a technique developed for SCN tissue culture by Yamazaki et al. 8 . Finally, we demonstrate how transgenic tissue can be used for measuring expression of clock genes/proteins using dynamic luciferase reporter technology, a method that originally was used for circadian measurements by Geusz et al. 9. We here use SCN tissues from the transgenic knock-in PERIOD2::LUCIFERASE mice produced by Yoo et al. 10. The mice contain a fusion protein of PERIOD (PER) 2 and the firefly enzyme LUCIFERASE. When PER2 is translated in the presence of the substrate for luciferase, i.e. luciferin, the PER2 expression can be monitored as bioluminescence when luciferase catalyzes the oxidation of luciferin. The number of emitted photons positively correlates to the amount of produced PER2 protein, and the bioluminescence rhythms match the PER2 protein rhythm in vivo 10 . In this way the cyclic variation in PER2 expression can be continuously monitored real time during many days. The protocol we follow for tissue culturing and real-time bioluminescence recording has been thoroughly described by Yamazaki and Takahashi 11 .