Integrated Glass Microfluidics with Electrochemical Nanogap Electrodes

We present a framework for the fabrication of chip-based electrochemical nanogap sensors integrated with microfluidics. Instead of polydimethylsiloxane (PDMS), SU-8 aided adhesive bonding of silicon and glass wafers is used to implement parallel flow control. The fabrication process permits wafer-scale production with high throughput and reproducibility. Additionally, the monolithic structures allow simple electrical and fluidic connections, alleviating the need for specialized equipment. We demonstrate the utility of these flow-incorporated nanogap sensors by performing redox cycling measurements under laminar flow conditions.</p

One-Watt level mid-IR output, singly resonant, continuous-wave optical parametric oscillator pumped by a monolithic diode laser

We report more than 1.1 Watt of idler power at 3373 nm in a singly resonant optical parametric oscillator (SRO), directly pumped by a single-frequency monolithic tapered diode laser. The SRO is based on a periodically poled MgO:LiNbO3 crystal in a four mirror cavity and is excited by 8.05 W of 1062 nm radiation. The SRO pump power at threshold is 4 W. The internal slope-efficiency and conversion efficiency reach 89% and 44% respectively. The signal and idler waves are temperature tuned in the range of 1541 to 1600 nm and 3154 to 3415 nm respectively. To the best of our knowledge, this is the highest output obtained for a diode pumped optical parametric oscillator (OPO), and the first time a SRO is directly pumped by a monolithic tapered diode laser

Stochastic Electrical Detection of Single Ion-Gated Semiconducting Polymers

Semiconducting polymer chains constitute the building blocks for a wide range of electronic materials and devices. However, most of their electrical characteristics at the single-molecule level have received little attention. Elucidating these properties can help understanding performance limits and enable new applications. Here, coupled ionic–electronic charge transport is exploited to measure the quasi-1D electrical current through long single conjugated polymer chains as they form transient contacts with electrodes separated by ≈10 nm. Fluctuations between internal conformations of the individual polymers are resolved as abrupt, multilevel switches in the electrical current. This behavior is consistent with the theoretical simulations based on the worm-like-chain (WLC) model for semiflexible polymers. In addition to probing the intrinsic properties of single semiconducting polymer chains, the results provide an unprecedented window into the dynamics of random-coil polymers and enable the use of semiconducting polymers as electrical labels for single-molecule (bio)sensing assays.</p

Incoherently pumped continuous wave optical parametric oscillator broadened by non-collinear phasematching

In this paper, we report on a singly resonant optical parametric oscillator (OPO) pumped by an amplified spontaneous emission (ASE) source. The pump focusing conditions allow non-collinear phasematching, which resulted in a 230 nm (190 cm$^{-1}$) spectral bandwidth. Calculations indicate that such phasematching schemes may be used to further broaden OPO spectral bandwidths.Comment: 7 pages 4 figure

PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients

Glucose-6-Phosphate Dehydrogenase Deficiency, Chlorproguanil-Dapsone with Artesunate and Post-treatment Haemolysis in African children treated for uncomplicated Malaria

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria

Electrochemical nanofluidic assays in the absence of reference electrode

Implementing a reliable reference electrode in miniaturized electrochemical sensors is challenging. Here, we present an alternative approach, based on redox cycling within a nanogap sensor consisting of two parallel electrodes, in which the reference electrode is omitted altogether. We show that on disconnection of the reference electrode, the solution potential floats to a certain value, which is explored theoretically and experimentally in order to quantitatively predict the potential. The obtained results are in good agreement with the theoretically reconstituted results

Single-molecule electrochemistry in nanochannels: probing the time of first passage

The diffusive mass transport of individual redox molecules was probed experimentally in microfabricated nanogap electrodes. The residence times for molecules inside a well-defined detection volume were extracted and the resulting distribution was compared with quantitative analytical predictions from random-walk theory for the time of first passage. The results suggest that a small number of strongly adsorbing sites strongly influence mass transport at trace analyte levels

Mitochondrial oxygen tension within the heart

By using a newly developed optical technique which enables non-invasive measurement of mitochondrial oxygenation (mitoPO2) in the intact heart, we addressed three long-standing oxygenation questions in cardiac physiology: 1) what is mitoPO2 within the in vivo heart?, 2) is mitoPO2 heterogeneously distributed?, and 3) how does mitoPO2 of the isolated Langendorff-perfused heart compare with that in the in vivo working heart? Following calibration and validation studies of the optical technique in isolated cardiomyocytes, mitochondria and intact hearts, we show that in the in vivo condition mean mitoPO2 was 35 ± 5 mm Hg. The mitoPO2 was highly heterogeneous, with the largest fraction (26%) of mitochondria having a mitoPO2 between 10 and 20 mm Hg, and 10% between 0 and 10 mm Hg. Hypoxic ventilation (10% oxygen) increased the fraction of mitochondria in the 0–10 mm Hg range to 45%, whereas hyperoxic ventilation (100% oxygen) had no major effect on mitoPO2. For Langendorff-perfused rat hearts, mean mitoPO2 was 29 ± 5 mm Hg with the largest fraction of mitochondria (30%) having a mitoPO2 between 0 and 10 mm Hg. Only in the maximally vasodilated condition, did the isolated heart compare with the in vivo heart (11% of mitochondria between 0 and 10 mm Hg). These data indicate 1) that the mean oxygen tension at the level of the mitochondria within the heart in vivo is higher than generally considered, 2) that mitoPO2 is considerably heterogeneous, and 3) that mitoPO2 of the classic buffer-perfused Langendorff heart is shifted to lower values as compared to the in vivo heart