Multisite Dopamine Sensing With Femtomolar Resolution Using a CMOS Enabled Aptasensor Chip.

Many biomarkers including neurotransmitters are found in external body fluids, such as sweat or saliva, but at lower titration levels than they are present in blood. Efficient detection of such biomarkers thus requires, on the one hand, to use techniques offering high sensitivity, and, on the other hand, to use a miniaturized format to carry out diagnostics in a minimally invasive way. Here, we present the hybrid integration of bottom-up silicon-nanowire Schottky-junction FETs (SiNW SJ-FETs) with complementary-metal-oxide-semiconductor (CMOS) readout and amplification electronics to establish a robust biosensing platform with 32 × 32 aptasensor measurement sites at a 100 µm pitch. The applied hetero-junctions yield a selective biomolecular detection down to femtomolar concentrations. Selective and multi-site detection of dopamine is demonstrated at an outstanding sensitivity of ∼1 V/fM. The integrated platform offers great potential for detecting biomarkers at high dilution levels and could be applied, for example, to diagnosing neurodegenerative diseases or monitoring therapy progress based on patient samples, such as tear liquid, saliva, or eccrine sweat.

Pollen exposure is associated with risk of respiratory symptoms during the first year of life.

BACKGROUND: Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and whether maternal atopy, infant's sex or air pollution modifies this association. METHODS: We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMMs). Effect modification by maternal atopy, infant's sex, and air pollution (NO2 , PM2.5 ) was assessed with interaction terms. RESULTS: Per infant, 37 ± 2 (mean ± SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m3 : combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM2.5 was found (p-value 0.003). CONCLUSION: Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma.

Real-time breath analysis of exhaled compounds upon peppermint oil ingestion by secondary electrospray ionization-high resolution mass spectrometry: technical aspects.

Breath analysis by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) has potential for clinical diagnosis and drug monitoring. However, there is still a lack of benchmarking data that shows the capability of this technique and allows comparability with other breath analysis techniques. In this regard, the goal of this study was the identification of volatile compounds upon ingestion of a specific peppermint oil capsule to get benchmark data for real-time breath analysis with SESI-HRMS. This was done in the framework of a consortium set up by the International Association of Breath Research (IABR), aimed at comparing several analytical instruments for breath analysis. Breath temporal profiles of two subjects were analyzed with SESI-HRMS before and after ingestion of a peppermint oil capsule. The measurements were performed at two different locations using identical SESI-HRMS platforms to allow for comparability and benchmarking. Remarkably, along with the four major compounds (monoterpenes/cineole, menthone, menthofuran and menthol) reported by other members of the consortium, we detected 57 additional features significantly associated (ρ > 0.8) with the peppermint oil capsule, suggesting that this relatively simple intervention might trigger a more complex metabolic cascade than initially expected. This observation was made on both sites. Additional replicate experiments for one of the subjects suggested that a core of 35-40 unique molecules are consistently detected in exhaled breath upon ingestion of the capsule. In addition, we illustrate the analytical capabilities of real-time SESI-HRMS/MS to assist in the identification of unknown compounds. The results outlined herein showcase the performance of SESI-HRMS and enable comparison with other breath analysis techniques. Along with that, they strengthen the potential of this analytical technique for non-invasive drug monitoring and clinical diagnostic purposes.

Carbon-Nanotube-Based Monolithic CMOS Platform for Electrochemical Detection of Neurotransmitter Glutamate.

We present a monolithic biosensor platform, based on carbon-nanotube field-effect transistors (CNTFETs), for the detection of the neurotransmitter glutamate. We used an array of 9'216 CNTFET devices with 96 integrated readout and amplification channels that was realized in complementary metal-oxide semiconductor technology (CMOS). The detection principle is based on amperometry, where electrochemically active hydrogen peroxide, a product of the enzymatic reaction of the target analyte and an enzyme that was covalently bonded to the CNTFET, modulated the conductance of the CNTFET-based sensors. We assessed the performance of the CNTs as enzymatic sensors by evaluating the minimal resolvable concentration change of glutamate in aqueous solutions. The minimal resolvable concentration change amounted to 10 µM of glutamate, which was one of the best values reported for CMOS-based systems so far.

Immediate effects of phototherapy on sleep in very preterm neonates: an observational study.

Process C (internal clock) and Process S (sleep-wake homeostasis) are the basis of sleep-wake regulation. In the last trimester of pregnancy, foetal heart rate is synchronized with the maternal circadian rhythm. At birth, this interaction fails and an ultradian rhythm appears. Light exposure is a strong factor influencing the synchronization of sleep-wake processes. However, little is known about the effects of phototherapy on the sleep rhythm of premature babies. It was hypothesized that sleep in preterm infants would not differ during phototherapy, but that a maturation effect would be seen. Sleep states were studied in 38 infants born < 32 weeks gestational age and/or < 1 500 g birth weight. Videos of 3 h were taken over the first 5 days of life. Based on breathing and movement patterns, behavioural states were defined as: awake; active sleep; or quiet sleep. Videos with and without phototherapy were compared for amounts of quiet sleep and active states (awake + active sleep). No significant association between phototherapy and amount of quiet sleep was found (P = 0.083). Analysis of videos in infants not under phototherapy revealed an increase in time spent awake with increasing gestational age. The current data suggest that the ultradian rhythm of preterm infants seems to be independent of phototherapy, supporting the notion that sleep rhythm in this population is mainly driven by their internal clock.

Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants.

In a prospective healthy birth cohort, we determined whether levels of exhaled nitric oxide (eNO) in healthy unselected infants at the age of 1 month were associated with maternal atopic disease and prenatal and early postnatal environmental exposures. Tidal eNO was measured in 98 healthy, unsedated infants (35 from mothers with atopy) (mean age +/- SD, 36.0 +/- 6.2 days) and was compared with histories taken in standardized interviews. eNO was higher in males compared with females (17.7 vs. 14.6 ppb, p = 0.042) and infants exposed to postnatal maternal smoking (+4.4 ppb, p = 0.027), adjusting for weight and tidal breathing parameters. Prenatal tobacco exposure was associated with higher eNO (+12.0 ppb, p = 0.01) in infants of mothers with asthma and lower eNO (-5.7 ppb) in infants of mothers without asthma (p for interaction < 0.0001). Coffee consumption in pregnancy decreased eNO (-6.0 ppb, p = 0.008) only in children of mothers with atopy (p for interaction = 0.015). Paternal atopy had no influence. In the early phase of immunologic development, before the onset of infections and allergic disease, the effect of prenatal or early postnatal environmental factors on eNO was modified by the presence of maternal atopic disease. This underlines the complex interaction of maternal and environmental factors in the development of airway disease.