Optical glucose sensor for single use microfluidic reactors

Glucose measurements are of tremendous interest in biotechnology. Electrochemical and optical methods to measure glucose have been intensively investigated in the last 30 years, in particular for medical diagnostics. A widely used principle is to measure the consumption of oxygen during the oxidation process of glucose facilitated by the enzyme glucose oxidase. The determination of glucose is based on a correlation between the oxygen consumption and the glucose concentration. In our contribution, we demonstrate the integration of a flow-through glucose sensor into microfluidic devices for cell culturing. The sensor consists of three layers: an oxygen sensitive layer, an enzymatic glucose-oxidase layer for glucose induced oxygen consumption and a diffusion layer. The oxygen sensitive layer contains polystyrene particles stained with meso-tetra(4-fluorophenyl)tetrabenzoporphyrin (PtTPTBPF4) embedded in a swellable hydrogel. The second layer contains aggregates of the enzyme glucose oxidase embedded in the same hydrogel. The last and final layer is a plain hydrogel diffusion barrier. By increasing the layer height of the diffusion layer, the dynamic range of the sensor can be tuned. Please click Additional Files below to see the full abstract

Monitoring of metabolic parameters of mammal cells cultures in microfluidic devices using integrated optical chemical sensors

Optical chemical sensors are well established in the chemical industry, life science, biotechnology and research laboratories. They are operate non-invasive, do not need any reference elements and can be read-out via contactless measurement. Moreover, it is possible to miniaturize and integrate them into microfluidic systems. Due to their simple composition, optical sensors can be produced at low price and therefore represent a good alternative compared to electrochemical sensors for their application in disposable microfluidics. The various possibilities of integrated optical oxygen sensors have already shown their potential in different microfluidic applications [1]. However, monitoring of further metabolic parameters is important for a better understanding of biological processes. Therefore, our group develops, next to oxygen sensors, also optical sensors for monitoring pH, glucose, CO2, ammonia and various ions. Still, integration in a Lab-on-a-chip format is a challenging task due to the state-of-the-art performances in terms of signal brightness, response times, optoelectronic read-out systems, fabrication and integration. Please click Additional Files below to see the full abstrac

PTR-MS studies of the reactions of H₃O⁺ with a number of deuterated volatile organic compounds and the subsequent sequential reactions of the primary product ions with water under normal and humid drift tube conditions::implications for use of deuterated compounds for breath analysis

Product ion distributions resulting from the primary reactions of H3O+ with nine D-labeled volatile organic compounds and the subsequent sequential reactions with H2O have been determined using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF 8000 (IONICON Analytik GmbH)) at various reduced electric field (E/N) values ranging from 80 up to 150 Td and for two different absolute humidity levels of air sample < 0.1% and 5%. The specific D-labeled compounds used in this study are acetone-d6, toluene-d8, benzene-d6, ethanol-d (C2H5OD), ethanol-d2 (CH3CD2OH), ethanol-d6, 2-propanol-d8, 2-propanol-d3 (CD3CH(OH)CH3), and isoprene-d5 (CH2CHC(CD2)CD3). With the exception of the two 2-propanol compounds, non-dissociative proton transfer is the dominant primary reaction pathway. For 2-propanol-d8 and 2-propanol-d3 the major primary reaction channel involved is dissociative proton transfer. However, unlike their undeuterated counterparts, the primary product ions undergo subsequent deuterium/hydrogen isotope exchange reactions with the ever present water in the drift tube, the extent of which of course depends on the humidity within that tube. This exchange leads to the generation of various isotopologue product ions, the product ion branching percentages of which are also dependent on the humidity in the drift tube. This results in complex mass spectra and the distribution of product ions leads to issues of reduced sensitivity and accuracy. However, the effect of D/H exchange considerably varies between the compounds under study. In the case of acetone-d6 it is very weak (<1%), because the exchange process is not facile when the deuterium is in the methyl functional group. In comparison, the H3O+/ benzene-d6 (C6D6) reaction and sequential reactions with water result in the production of the isotopologue ions C6Dn(H7-n)+ (where n = 0–6). Changing the value of E/N and/or the humidity in the drift tube considerably affects the amount of the isotope exchange reactions and hence the resulting sequential product ion distributions. An important conclusion of the findings from this work is that care must be taken in the choice of an exogenous deuterated compound for use in breath pharmacokinetic studies using proton transfer reaction mass spectrometry; otherwise the resulting D/H exchange processes impose interpretative problems. © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

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

Real-time Neurofeedback Using Functional MRI Could Improve Down-Regulation of Amygdala Activity During Emotional Stimulation: A Proof-of-Concept Study

The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

Background DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. Objective To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. Methods We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. Results First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. Conclusions STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

BACKGROUND DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. OBJECTIVE To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. METHODS We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. RESULTS First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. CONCLUSIONS STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features