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.

Postprandial hypertriglyceridemia and oxidative stress in patients of type 2 diabetes mellitus with macrovascular complications.

BACKGROUND: Oxidative stress has been implicated in vascular complications of diabetes mellitus (DM). This study aims to evaluate the relationship between postprandial hypertriglyceridemia (PP-HTG) and oxidative stress in Indian patients of type 2 DM with macrovascular complications. METHODS: Plasma triglycerides (TG), thiobarbituric acid reactive substances (TBARS), erythrocyte reduced glutathione (GSH) and superoxide dismutase (SOD) were measured in fasting and postprandial (PP) state at 2, 4, 6 and 8 h after a high fat meal challenge in controls (Group I) and patients of type 2 DM without (Group II) and with macrovascular complications (Group III). RESULTS: Postprandial TGs increased significantly in patients with type 2 DM, which showed an exaggerated response to high fat meal challenge in Group III as compared to Group II. Highest PP-TBARS were also observed in Group III which correlated positively with TG. However, GSH and SOD were lower in both groups of diabetics as compared to controls. CONCLUSIONS: The magnitude of PP-HTG appears to be the major determinant of oxidative stress in type 2 DM, which along with a compromised antioxidant status may lead to endothelial dysfunction and macrovascular complications.