Mass Spectrometric Study of the Ionized C60: (Gamma-Cyclodextrin)2 Inclusion Complex by Collision Induced Dissociation

The water soluble inclusion complex [C(60):(gamma-cyclodextrin)(2)] has been characterized using electrospray tandem mass spectrometry and collision induced dissociation. [C(60):(gamma-cyclodextrin)(2)] ions were detected in the gas phase as doubly deprotonated, doubly protonated and doubly sodiated ions. The absence of monocharged complex ions following electronebulization is a likely consequence of the dimeric nature and structural symmetry of the inclusion complex. The collision induced dissociation of positive ions led exclusively to the observation of the protonated and sodiated cyclodextrin ions as well as their fragments. In negative ion mode the closed shell anion C(60)H(-) was the dominant fragment detected at low collision energies whereas at higher collision energies the signal corresponding to deprotonated cyclodextrin units becomes significant. Since C(60) (2-) has been reported to have a nonnegligible basicity compared to C(60) and C(60) (-), it is likely that the proton transfer involved in the formation of the C(60)H(-) anion occurs following transfer of the two electrons from the deprotonated gamma-cyclodextrins to the fullerene. Finally, the charge state of the inclusion complex ions is also shown to affect the interaction strengths between its subunits. The relative stabilities of the three ionic species studied in gas phase following electronebulization are as follows: [C(60):(gamma-cyclodextrin)(2) + 2H](2+) < [C(60):(gamma-cyclodextrin)(2)- 2H](2-) < [C(60):(gamma-cyclodextrin)(2) + 2Na](2+).NOMAD

Neurovascular unit on a chip: implications for translational applications

The blood–brain barrier (BBB) dynamically controls exchange between the brain and the body, but this interaction cannot be studied directly in the intact human brain or suffi ciently represented by animal models. Most existing in vitro BBB models do not include neurons and glia with other BBB elements and do not adequately predict drug effi cacy and toxicity. Under the National Institutes of Health Microtissue Initiative, we are developing a threedimensional, multicompartment, organotypic microphysiological system representative of a neurovascular unit of the brain. The neurovascular unit system will serve as a model to study interactions between the central nervous system neurons and the cerebral spinal fl uid (CSF) compartment, all coupled to a realistic blood-surrogate supply and venous return system that also incorporates circulating immune cells and the choroid plexus. Hence all three critical brain barriers will be recapitulated: blood–brain, brain–CSF, and blood–CSF. Primary and stem cell-derived human cells will interact with a variety of agents to produce critical chemical communications across the BBB and between brain regions. Cytomegalovirus, a common herpesvirus, will be used as an initial model of infections regulated by the BBB. This novel technological platform, which combines innovative microfl uidics, cell culture, analytical instruments, bioinformatics, control theory, neuroscience, and drug discovery, will replicate chemical communication, molecular traffi cking, and infl ammation in the brain. The platform will enable targeted and clinically relevant nutritional and pharmacologic interventions for or prevention of such chronic diseases as obesity and acute injury such as stroke, and will uncover potential adverse eff ects of drugs. If successful, this project will produce clinically useful technologies and reveal new insights into how the brain receives, modifi es, and is aff ected by drugs, other neurotropic agents, and diseases

Organs-on-Chips as Bridges for Predictive Toxicology

The next generation of chemical toxicity testing will use organs-on-chips (OoCs)—3D cultures of heterotypic cells with appropriate extracellular matrices to better approximate the in vivo cellular microenvironment. Researchers are already working to validate whether OoCs are predictive of toxicity in humans. Here, we review two other key aspects of how OoCs may advance predictive toxicology—each taking advantage of OoCs as systems of intermediate complexity that remain experimentally accessible. First, the intermediate complexity of OoCs will help elucidate the scale(s) of organismal complexity that currently confound computational predictions of in vivo toxicity from in vitro data sets. Identifying the strongest confounding factors will help researchers improve the computational models underlying such predictions. Second, the experimental accessibility of OoCs will allow researchers to analyze chemical-exposure responses in OoCs using an array of high-content readouts—from fluorescent biosensors that report dynamic changes in specific cell signaling pathways to unbiased searches over broader biochemical space using technologies like ion mobility-mass spectrometry. Such high-content information on OoC responses will help determine the details of adverse outcome pathways. We note these possible uses of OoCs so that researchers and engineers can consider them in the design of next-generation OoC control, perfusion, and analysis platforms

Controlled insulator-to-metal transformation in printable polymer composites with nanometal clusters

10.1038/nmat1806Nature Materials62149-15

Electrochemical biosensors - sensor principles and architectures

Quantification of biological or biochemical processes are of utmost importancefor medical, biological and biotechnological applications. However, converting the biologicalinformation to an easily processed electronic signal is challenging due to the complexity ofconnecting an electronic device directly to a biological environment. Electrochemical biosensorsprovide an attractive means to analyze the content of a biological sample due to thedirect conversion of a biological event to an electronic signal. Over the past decades severalsensing concepts and related devices have been developed. In this review, the most commontraditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry,impedance spectroscopy, and various field-effect transistor based methods are presented alongwith selected promising novel approaches, such as nanowire or magnetic nanoparticle-basedbiosensing. Additional measurement techniques, which have been shown useful in combinationwith electrochemical detection, are also summarized, such as the electrochemical versionsof surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry,quartz crystal microbalance, and scanning probe microscopy.The signal transduction and the general performance of electrochemical sensors are often determinedby the surface architectures that connect the sensing element to the biological sampleat the nanometer scale. The most common surface modification techniques, the various electrochemicaltransduction mechanisms, and the choice of the recognition receptor moleculesall influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches,such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymesinto vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities forsignal amplification.In particular, this review highlights the importance of the precise control over the delicateinterplay between surface nano-architectures, surface functionalization and the chosen sensortransducer principle, as well as the usefulness of complementary characterization tools tointerpret and to optimize the sensor response