Guenter Roth

Neurological symptoms in patients with biopsy proven celiac disease

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 ± 15 years, mean disease duration 8 ± 11 years) were recruited through advertisements. All participants adhered to a gluten‐free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten‐free diet.

Semi-contact-writing of polymer molds for prototyping PDMS chips with low surface roughness, sharp edges and locally varying channel heights

Microfluidic systems fabricated in polydimethylsiloxane (PDMS) enable a broad variety of applications and are widespread in the field of Lab-on-a-Chip. Here we demonstrate semi-contact-writing, a novel method for fabrication of polymer based molds for casting microfluidic PDMS chips in a highly flexible, time and cost-efficient manner. The method is related to direct-writing of an aqueous polymer solution on a planar glass substrate and substitutes conventional, time- and cost-consuming UV-lithography. This technique facilitates on-demand prototyping in a low-cost manner and is therefore ideally suited for rapid chip layout iterations. No cleanroom facilities and less expertise are required. Fabrication time from scratch to ready-to-use PDMS-chip is less than 5?h. This polymer writing method enables structure widths down to 140 ?m and controllable structure heights ranging from 5.5 ?m for writing single layers up to 98 ?m by stacking. As a unique property, freely selectable height variations across a substrate can be achieved by application of local stacking. Furthermore, the molds exhibit low surface roughness (R a ??=??24?nm, R RMS??=??28?nm) and high fidelity edge sharpness. We validated the method by fabrication of molds to cast PDMS chips for droplet based flow-through PCR with single-cell sensitivity.

Low-Volume Label-Free Detection of Molecule-Protein Interactions on Microarrays by Imaging Reflectometric Interferometry.

This system allows the high-throughput protein interaction analysis on microarrays. We apply the interference technology 1λ–imaging reflectometric interferometry (iRIf) as a label-free detection method and create microfluidic flow cells in microscope slide format for low reagent consumption and lab work compatibility. By now, most prominent for imaging label-free interaction analyses on microarrays are imaging surface plasmon resonance (SPR) methods, quartz crystal microbalance, or biolayer interferometry. SPR is sensitive against temperature drifts and suffers from plasmon crosstalk, and all systems lack array size (maximum 96 spots). Our detection system is robust against temperature drifts. Microarrays are analyzed with a spatial resolution of 7 µm and time resolution of ≤50 fps. System sensitivity is competitive, with random noise of <5 × 10−5 and baseline drift of <3 × 10−6. Currently available spotting technologies limit array sizes to ~4 spots/mm2 (1080 spots/array); our detection system would allow ~40 spots/mm2 (10,800 spots/array). The microfluidic flow cells consist of structured PDMS inlays sealed by versatilely coated glass slides immobilizing the microarray. The injection protocol determines reagent volumes, priming rates, and flow cell temperatures for up to 44 reagents; volumes of ≤300 µL are validated. The system is validated physically by the biotinylated bovine serum albumin streptavidin assay and biochemically by thrombin aptamer interaction analysis, resulting in a KD of ~100 nM.