Online analysis of oxygen inside silicon-glass microreactors with integrated optical sensors

AbstractA powerful online analysis set-up for oxygen measurements within microfluidic devices is presented. It features integration of optical oxygen sensors into microreactors, which enables contactless, accurate and inexpensive readout using commercially available oxygen meters via luminescent lifetime measurements in the frequency domain (phase shifts). The fabrication and patterning of sensor layers down to a size of 100μm in diameter is performed via automated airbrush spraying and was used for the integration into silicon-glass microreactors. A novel and easily processable sensor material is also presented and consists of a polystyrene- silicone rubber composite matrix with embedded palladium(II) or platinum(II) meso-tetra(4-fluorophenyl) tetrabenzoporphyrin (PdTPTBPF and PtTPTBPF) as oxygen sensitive dye. The resulting sensor layers have several advantages such as being excitable with red light, emitting in the near-infrared spectral region, being photostable and covering a wide oxygen concentration range. The trace oxygen sensor (PdTPTBPF) in particular shows a resolution of 0.06–0.22hPa at oxygen concentrations lower than 20hPa (<2% oxygen) and the normal range oxygen sensor (PtTPTBPF) shows a resolution of 0.2–0.6hPa at low oxygen concentrations (<50hPa) and 1–2hPa at ambient air oxygen concentrations. The sensors were integrated into different silicon-glass microreactors which were manufactured using mass production compatible processes. The obtained microreactors were applied for online monitoring of enzyme transformations, including d-alanine or d-phenylalanine oxidation by d-amino acid oxidase, and glucose oxidation by glucose oxidase

Microfluidic-Based Detection of AML-Specific Biomarkers Using the Example of Promyelocyte Leukemia

A microfluidic assay for the detection of promyelocytic leukemia (PML)-retinoic acid receptor &alpha; (RAR&alpha;) fusion protein was developed. This microfluidic-based system can be used for rapid personalized differential diagnosis of acute promyelocyte leukemia (APL) with the aim of early initiation of individualized therapy. The fusion protein PML-RAR&alpha; occurs in 95% of acute promyelocytic leukemia cases and is considered as diagnostically relevant. The fusion protein is formed as a result of translocation t(15,17) and is detected in the laboratory by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR). Diagnostic methods require many laboratory steps with specialized staff. The developed microfluidic assay includes a sandwich enzyme-linked immunosorbent assay (ELISA) system for PML-RAR&alpha; on surface of magnetic microparticles in a microfluidic chip. A rapid detection of PML-RAR&alpha; in cell lysates is achieved in less than one hour. A biotinylated PML-antibody on the surface of magnetic streptavidin coated microparticles is used as capture antibody. The bound translocation product is detected by a RAR&alpha; antibody conjugated with horseradish peroxidase and the substrate QuantaRed. The analysis is performed in microfluidic channels which involves automated liquid processing with stringent washing and short incubation times. The results of the developed assay show that cell lysates of PML-RAR&alpha;-positive cells (NB-4) can be clearly distinguished from PML-RAR&alpha;-negative cells (HL-60, MV4-11)

Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions

Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project

BACKGROUND: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. METHODS: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. RESULTS: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. CONCLUSIONS: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype

MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Background: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype