Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Targeting Arousal and Sleep through Noninvasive Brain Stimulation to Improve Mental Health.

Arousal and sleep represent fundamental physiological domains, and alterations in the form of insomnia (difficulty falling or staying asleep) or hypersomnia (increased propensity for falling asleep or increased sleep duration) are prevalent clinical problems. Current first-line treatments include psychotherapy and pharmacotherapy. Despite significant success, a number of patients do not benefit sufficiently. Progress is limited by an incomplete understanding of the -neurobiology of insomnia and hypersomnia. This work summarizes current concepts of the regulation of arousal and sleep and its modulation through noninvasive brain stimulation (NIBS), including transcranial magnetic, current, and auditory stimulation. Particularly, we suggest: (1) characterization of patients with sleep problems - across diagnostic entities of mental disorders - based on specific alterations of sleep, including alterations of sleep slow waves, sleep spindles, cross-frequency coupling of brain oscillations, local sleep-wake regulation, and REM sleep and (2) targeting these with specific NIBS techniques. While evidence is accumulating that the modulation of specific alterations of sleep through NIBS is feasible, it remains to be tested whether this translates to clinically relevant effects and new treatment developments.