Towards a Miniaturized Photoacoustic Sensor for Transcutaneous CO2 Monitoring.

A photoacoustic sensor system (PAS) intended for carbon dioxide (CO2) blood gas detection is presented. The development focuses on a photoacoustic (PA) sensor based on the so-called two-chamber principle, i.e., comprising a measuring cell and a detection chamber. The aim is the reliable continuous monitoring of transcutaneous CO2 values, which is very important, for example, in intensive care unit patient monitoring. An infrared light-emitting diode (LED) with an emission peak wavelength at 4.3 µm was used as a light source. A micro-electro-mechanical system (MEMS) microphone and the target gas CO2 are inside a hermetically sealed detection chamber for selective target gas detection. Based on conducted simulations and measurement results in a laboratory setup, a miniaturized PA CO2 sensor with an absorption path length of 2.0 mm and a diameter of 3.0 mm was developed for the investigation of cross-sensitivities, detection limit, and signal stability and was compared to a commercial infrared CO2 sensor with a similar measurement range. The achieved detection limit of the presented PA CO2 sensor during laboratory tests is 1 vol. % CO2. Compared to the commercial sensor, our PA sensor showed less influences of humidity and oxygen on the detected signal and a faster response and recovery time. Finally, the developed sensor system was fixed to the skin of a test person, and an arterialization time of 181 min could be determined.

Co3O4-Based Materials as Potential Catalysts for Methane Detection in Catalytic Gas Sensors.

The present work deals with the development of Co3O4-based catalysts for potential application in catalytic gas sensors for methane (CH4) detection. Among the transition-metal oxide catalysts, Co3O4 exhibits the highest activity in catalytic combustion. Doping Co3O4 with another metal can further improve its catalytic performance. Despite their promising properties, Co3O4 materials have rarely been tested for use in catalytic gas sensors. In our study, the influence of catalyst morphology and Ni doping on the catalytic activity and thermal stability of Co3O4-based catalysts was analyzed by differential calorimetry by measuring the thermal response to 1% CH4. The morphology of two Co3O4 catalysts and two NixCo3-xO4 with a Ni:Co molar ratio of 1:2 and 1:5 was studied using scanning transmission electron microscopy and energy dispersive X-ray analysis. The catalysts were synthesized by (co)precipitation with KOH solution. The investigations showed that Ni doping can improve the catalytic activity of Co3O4 catalysts. The thermal response of Ni-doped catalysts was increased by more than 20% at 400 °C and 450 °C compared to one of the studied Co3O4 oxides. However, the thermal response of the other Co3O4 was even higher than that of NixCo3-xO4 catalysts (8% at 400 °C). Furthermore, the modification of Co3O4 with Ni simultaneously brings stability problems at higher operating temperatures (≥400 °C) due to the observed inhomogeneous Ni distribution in the structure of NixCo3-xO4. In particular, the NixCo3-xO4 with high Ni content (Ni:Co ratio 1:2) showed apparent NiO separation and thus a strong decrease in thermal response of 8% after 24 h of heat treatment at 400 °C. The reaction of the Co3O4 catalysts remained quite stable. Therefore, controlling the structure and morphology of Co3O4 achieved more promising results, demonstrating its applicability as a catalyst for gas sensing.

An adaptive soft-sensor for advanced real-time monitoring of an antibody-drug conjugation reaction.

In the production of antibody-drug conjugates (ADCs), the conjugation reaction is a central step defining the final product composition and, hence, directly affecting product safety and efficacy. To enable real-time monitoring, spectroscopic sensors in combination with multivariate regression models have gained popularity in recent years. The extended Kalman filter (EKF) can be used as so-called soft-sensor to fuse sensor predictions with long-horizon forecasts by process models. This enables the dynamic update of the current state and provides increased robustness against experimental noise or model errors. Due to the uncertainty associated with sensor and process models in biopharmaceutical applications, the deployment of such soft-sensors is challenging. In this study, we demonstrate the combination of an uncertainty-aware sensor model with a kinetic reaction model using an EKF to monitor a site-directed ADC conjugation reaction. As the sensor model, a Gaussian process regression model is presented to realize a time-variant determination of the sensor uncertainty. The EKF fuses the time-discrete predictions of the amount of conjugated drug from the sensor model with the time-continuous predictions from the kinetic model. While the ADC species are not distinguishable by on-line recorded UV/Vis spectra, the developed soft-sensor is able to dynamically update all relevant reaction species. It could be shown that the use of time-variant process and sensor noise computation approaches improved the performance of the EKF and achieved a reduction of the prediction error of up to 23% compared with the kinetic model. The developed framework proved to enhance robustness against noisy sensor measurements or wrong model initialization and was successfully transferred from batch to fed-batch mode. In future, this framework could be implemented for model-based process control and be adopted for other ADC conjugation reaction types.

Detection of SO2F2 Using a Photoacoustic Two-Chamber Approach.

The wide use of sulfuryl difluoride (SO2F2) for termite control in buildings, warehouses and shipping containers requires the implementation of suitable sensors for reliable detection. SO2F2 is highly toxic to humans and the environment, and moreover, it is a potent greenhouse gas. We developed two photoacoustic two-chamber sensors with the aim to detect two different concentration ranges, 0-1 vol.-% SO2F2 and 0-100 ppm SO2F2, so that different applications can be targeted: the sensor for high concentrations for the effective treatment of buildings, containers, etc., and the sensor for low concentrations as personal safety device. Photoacoustic detectors were designed, fabricated, and then filled with either pure SO2F2 or pure substituent gas, the refrigerant R227ea, to detect SO2F2. Absorption cells with optical path lengths of 50 mm and 1.6 m were built for both concentration ranges. The sensitivity to SO2F2 as well as cross-sensitivities to CO2 and H2O were measured. The results show that concentrations below 1 ppm SO2F2 can be reliably detected, and possible cross-sensitivities can be effectively compensated.

Towards a Miniaturized Photoacoustic Detector for the Infrared Spectroscopic Analysis of SO2F2 and Refrigerants.

Sulfuryl fluoride (SO2F2) is a toxic and potent greenhouse gas that is currently widely used as a fumigant insecticide in houses, food, and shipping containers. Though it poses a major hazard to humans, its detection is still carried out manually and only on a random basis. In this paper, we present a two-chamber photoacoustic approach for continuous SO2F2 sensing. Because of the high toxicity of SO2F2, the concept is to use a non-toxic substituent gas with similar absorption characteristics in the photoacoustic detector chamber, i.e., to measure SO2F2 indirectly. The refrigerants R227ea, R125, R134a, and propene were identified as possible substituents using a Fourier-transform infrared (FTIR) spectroscopic analysis. The resulting infrared spectra were used to simulate the sensitivity of the substituents of a photoacoustic sensor to SO2F2 in different concentration ranges and at different optical path lengths. The simulations showed that R227ea has the highest sensitivity to SO2F2 among the substituents and is therefore a promising substituent detector gas. Simulations concerning the possible cross-sensitivity of the photoacoustic detectors to H2O and CO2 were also performed. These results are the first step towards the development of a miniaturized, sensitive, and cost-effective photoacoustic sensor system for SO2F2.

Anodically Bonded Photoacoustic Transducer: An Approach towards Wafer-Level Optical Gas Sensors.

We present a concept for a wafer-level manufactured photoacoustic transducer, suitable to be used in consumer-grade gas sensors. The transducer consists of an anodically bonded two-layer stack of a blank silicon wafer and an 11 µm membrane, which was wet-etched from a borosilicate wafer. The membrane separates two cavities; one of which was hermetically sealed and filled with CO2 during the anodic bonding and acts as an infrared absorber. The second cavity was designed to be connected to a standard MEMS microphone on PCB-level forming an infrared-sensitive photoacoustic detector. CO2 sensors consisting of the detector and a MEMS infrared emitter were built up and characterized towards their sensitivity and noise levels at six different component distance ranging from 3.0 mm to 15.5 mm. The signal response for the sample with the longest absorption path ranged from a decrease of 8.3% at a CO2 concentration of 9400 ppm to a decrease of 0.8% at a concentration of 560 ppm. A standard deviation of the measured values of 18 ppm was determined when the sensor was exposed to 1000 ppm CO2.

On-Board Monitoring of SO2 Ship Emissions Using Resonant Photoacoustic Gas Detection in the UV Range.

A photoacoustic gas detector for SO2 was developed for ship exhaust gas emission monitoring. The basic measurement setup is based on the absorption of electromagnetic radiation of SO2 at 285 nm wavelength. A commercially available ultraviolet (UV) light-emitting diode (LED) is used as the light source and a micro-electro-mechanical system (MEMS) microphone as the detector. In order to achieve the required detection limits in marine applications, a measuring cell which allows an acoustically resonant amplification of the photoacoustic signal was developed and characterized. A limit of detection of 1 ppm was achieved in lab conditions during continuous gas flow. Long-term measurements on a container ship demonstrated the application relevance of the developed system.

Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer.

Genomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) and provided a comprehensive catalog of somatic mutations. However, the limited number of significant cancer-related genes obtained so far only partially explains the biological complexity of HNSCC and hampers the development of novel diagnostic biomarkers and therapeutic targets. We pursued a multiscale omics approach based on whole-exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO-HNC cohort (n = 87), and confirmed new findings with datasets from The Cancer Genome Atlas (TCGA). Promoter methylation was confirmed by MassARRAY analysis and protein expression was assessed by immunohistochemistry and immunofluorescence staining. We discovered a set of cancer-related genes with frequent somatic mutations and high frequency of promoter methylation. This included the ryanodine receptor 2 (RYR2), which showed variable promoter methylation and expression in both tumor samples and cell lines. Immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesion to invasive cancer and indicated that reduced RYR2 expression in adjacent tissue and precancerous lesions might serve as risk factor for unfavorable prognosis and upcoming malignant conversion. In summary, our data indicate that impaired RYR2 function by either somatic mutation or epigenetic silencing is a common event in HNSCC pathogenesis. Detection of RYR2 expression and/or promoter methylation might enable risk assessment for malignant conversion of dysplastic lesions.

Resonant Photoacoustic Spectroscopy of NO2 with a UV-LED Based Sensor.

Nitrogen dioxide (NO 2 ) is a poisonous trace gas that requires monitoring in urban areas. Accurate measurement in sub-ppm concentrations represents a wide application field for suitable economical sensors. We present a novel approach to measure NO 2 with a photoacoustic sensor using a T-shaped resonance cell. An inexpensive UV-LED with a peak wavelength of 405 nm as radiation source as well as a commercial MEMS microphone for acoustic detection were used. In this work, a cell has been developed that enables a "non-contact" feedthrough of the divergent LED beam. Thus, unwanted background noise due to absorption on the inside walls is minimized. As part of the development, an acoustic simulation has been carried out to find the resonance frequencies and to visualize the resulting standing wave patterns in various geometries. The pressure amplitude was calculated for different shapes and sizes. A model iteratively optimized in this way forms the basis of a construction that was built for gas measurement by rapid prototyping methods. The real resonance frequencies were compared to the ones found in simulation. The limit of detection was determined in a nitrogen dioxide measurement to be 200 ppb (6 σ ) for a cell made of aluminum.

Investigation of Gasochromic Rhodium Complexes Towards Their Reactivity to CO and Integration into an Optical Gas Sensor for Fire Gas Detection.

The detection of the toxic gas carbon monoxide (CO) in the low ppm range is required in different applications. We present a study of the reactivity of different gasochromic rhodium complexes towards the toxic gas carbon monoxide (CO). Therefore, variations of binuclear rhodium complexes with different ligands were prepared. They were characterized by FTIR spectroscopy, ¹H NMR spectroscopy, and differential scanning calorimetry. All complexes are spectroscopically distinguishable and temperature stable up to at least 187 °C. The gasochromic behavior of all different compounds was tested. Therefore, the compounds were dissolved in toluene and exposed to 100 ppm CO for 10 min to investigate their gas sensitivity and reaction velocity. The changes in the transmission spectra were recorded by UV/vis spectroscopy. Furthermore, a significant influence of the solvent to the color dyes’ gasochromic reaction and behavior was observed. After characterization, one complex was transferred as sensing element into an optical gas sensor. Two different measurement principles (reflection- and waveguide-based) were built up and tested towards their capability as gasochromic CO sensors. Finally, different gas-dependent measurements were carried out.

Towards Enhanced Gas Sensor Performance with Fluoropolymer Membranes.

In this paper we report on how to increase the selectivity of gas sensors by using fluoropolymer membranes. The mass transport of polar and non-polar gases through a polymer membrane matrix was studied by systematic selection of polymers with different degrees of fluorination, as well as polymers whose monomers have ether groups (-O-) in addition to fluorine groups (-F). For the study, a set of application-relevant gases including H2, CO, CO2, NO2, methane, ethanol, acetone, and acetaldehyde as well as various concentrations of relative humidity were used. These gases have different functional groups and polarities, yet have a similar kinetic diameter and are therefore typically difficult to separate. The concentrations of the gases were chosen according to international indicative limit values (TWA, STEL). To measure the concentration in the feed and permeate, we used tin-dioxide-based metal oxide gas sensors with palladium catalyst (SnO2:Pd), catalytic sensors (also SnO2:Pd-based) and thermal conductivity sensors. This allows a close examination of the interdependence of diffusion and physicochemical operating principle of the sensor. Our goal is to increase the selectivity of gas sensors by using inexpensive fluoropolymer membranes. The measurements showed that through membranes with low polarity, preferably non-polar gases are transported. Furthermore, the degree of crystallization influences the permeability and selectivity of a polymer membrane. Basically the polar polymers showed a higher permeability to water vapor and polar substances than non-polar polymer membranes.

Photoacoustic methane detection inside a MEMS microphone.

An innovative laser based photoacoustic (PA) gas sensing concept with intrinsic miniaturization potential was developed and investigated for methane trace gas detection. An interband cascade laser (ICL) with an optical power of 8.5 mW targets a methane (CH4) absorption line feature around 3057.7 cm-1 (or 3270 nm). The ICL was focused into the sound port of a MEMS microphone, where the PA signal was generated and detected using a wavelength modulation concept (2f-WMS-PAS). The MEMS microphone was successfully implemented as an intrinsically miniaturized PA cell being gas sensing volume, acoustic resonator and sound transducer at once. Frequencies between 2 kHz and 100 kHz were investigated and used for methane detection. A sensitive and resonant methane detection at 41.8 kHz was investigated by concentration variations between 0 and 10 ppm CH4 in N2. A limit of detection ( 3 σ -LOD) of 329 ppb was estimated. The long term stability of this sensor was investigated by the measurement of methane in ambient air. A noise equivalent concentration (NEC) of 14 ppb (parts per billion) at an average time of 10 s was estimated. This value corresponds to a normalized noise equivalent absorption (NNEA) of 2 ⋅ 1 0 - 8 W cm-1 Hz-1/2. Using the MEMS microphone directly as PA cell offers the possibility for an extremely miniaturized, highly sensitive and very cost-efficient photoacoustic trace gas sensor.

Towards Low Temperature Operation of Catalytic Gas Sensors: Mesoporous Co3O4-Supported Au-Pd Nanoparticles as Functional Material.

It is shown that the operating temperature of pellistors for the detection of methane can be reduced to 300 °C by using Au-Pd nanoparticles on mesoporous cobalt oxide (Au-Pd@meso-Co3O4). The aim is to reduce possible catalyst poisoning that occurs during the high-temperature operation of conventional Pd-based pellistors, which are usually operated at 450 °C or higher. The individual role of Au-Pd as well as Co3O4 in terms of their catalytic activity has been investigated. Above 300 °C, Au-Pd bimetallic particles are mainly responsible for the catalytic combustion of methane. However, below 300 °C, only the Co3O4 has a catalytic effect. In contrast to methane, the sensor response and the temperature increase of the sensor under propane exposure is much larger than for methane due to the larger heat of combustion of propane. Due to its lower activation energy requirement, propane exhibits a higher propensity for oxidation compared to methane. As a result, the detection of propane can be achieved at even lower temperatures due to its enhanced reactivity.

Optical waveguides for the evanescent wave-induced cleavage of photolabile linker compounds.

Functional surfaces and especially the control of surface properties depending on external parameters such as light illumination have gained increasing importance in the last few years. We present the characterization of polymers from the cycloolefin (co)polymer class (COC/COP) functionalized with an aminosilane as a basis for the further immobilization of compounds. In a first step, an assay using AlexaFluor®647 fluorescent dye was used to assess surface homogeneity and reproducibility. A coefficient of variation of less than 15% for dot-to-dot and less than 25% for chip-to-chip could be achieved. The same amino-functionalized surfaces were then used to immobilize a biotinylated photolabile linker compound, binding AlexaFluor®647-labeled streptavidin. The linker was photocleaved with high efficiency at λ = 365 nm and P = 0.15 mW/cm(2). Fluorescence measurements show that polymers of the COC/COP class can be used as versatile surfaces for the photoinduced release of compounds immobilized via photolabile linkers.

Cement pressurizing reduces radiolucent lines at glenoid: A randomized, multicentric study.

BACKGROUND: The hypothesis of this study is that cement pressurization into the glenoid reduces the rate of radiolucent lines in total shoulder arthroplasty in the mean 25.5 months after the operation. METHODS: To examine this effect, a multicentric prospective randomized study (level of evidence 1) was initiated: one group (group P, n = 24) received intraoperative pressurization of cement into the cancellous bone of the glenoid, the other cement without pressure (group NoP, n = 27). Inclusion criteria were an osteoarthritis with glenoid erosion <15° and an intact rotator cuff. RESULTS: There were no significant differences preoperatively between the groups regarding age (mean age 66 ± 10 years (range 44-81)), gender, range of motion, scores and pathomorphology. Both groups had a significant improvement of the scores, strength, motion and satisfaction 25.5 months after the intervention. The scores were similar between the groups (ns). However, cement pressurization at the glenoid side significantly reduced the incidence of radiolucent lines (p < 0.027). CONCLUSION: This supports the use of this simple technique to improve long-term survival of total shoulder arthroplasty.Level of evidence: 1.

Commentary regarding: "Activity determination of FAD-dependent glucose dehydrogenase immobilized in PEDOT: PSS-PVA composite films for biosensor applications".

In the light of continuous improvement and optimization, recent experiments that the authors conducted give new insights into the applied evaluation method of Riegel et al. [1]: Thorough investigations of the previous results regarding the usage of the Lowry Assay showed discrepancies in the determination of the released amount of protein in the analysis solution. The accurate quantification of this parameter is crucial as it directly influences the calculation of the residual enzymatic activity. In concrete terms, this finding has a major impact on the presented and discussed results in the article "Activity determination of FAD-dependent glucose dehydrogenase immobilized in PEDOT: PSS-PVA composite films for biosensor applications" [1]. Thus, this commentary addresses the new insights concerning the applied evaluation method, explains necessary revisions and discusses new conclusions derived from the adjusted evaluation method.

Resistance of mitochondrial p53 to dominant inhibition.

BACKGROUND: Mutation of a tumor suppressor allele leaves the second as backup. Not necessarily so with p53. This homo-tetrameric transcription factor can become contaminated with mutant p53 through hetero-tetramerization. In addition, it can be out-competed by the binding to p53 DNA recognition motifs of transactivation-incompetent isoforms (DeltaN and DeltaTA-isoforms) of the p53/p63/p73 family of proteins. Countermeasures against such dominant-negative or dominant-inhibitory action might include the evolutionary gain of novel, transactivation-independent tumor suppressor functions by the wild-type monomer. RESULTS: Here we have studied, mostly in human HCT116 colon adenocarcinoma cells with an intact p53 pathway, the effects of dominant-inhibitory p53 mutants and of Deltaex2/3p73, a tumor-associated DeltaTA-competitor of wild-type p53, on the nuclear transactivation-dependent and extra-nuclear transactivation-independent functions of wild-type p53. We report that mutant p53 and Deltaex2/3p73, expressed from a single gene copy per cell, interfere with the stress-induced expression of p53-responsive genes but leave the extra-nuclear apoptosis by mitochondrial p53 largely unaffected, although both wild-type and mutant p53 associate with the mitochondria. In accord with these observations, we present evidence that in contrast to nuclear p53 the vast majority of mitochondrial p53, be it wild-type or mutant, is consisting of monomeric protein. CONCLUSION: The extra-nuclear p53-dependent apoptosis may constitute a fail-safe mechanism against dominant inhibition.

Evanescent field Sensors Based on Tantalum Pentoxide Waveguides - A Review.

Evanescent field sensors based on waveguide surfaces play an important rolewhere high sensitivity is required. Particularly tantalum pentoxide (Ta2O5) is a suitablematerial for thin-film waveguides due to its high refractive index and low attenuation.Many label-free biosensor systems such as grating couplers and interferometric sensors aswell as fluorescence-based systems benefit from this waveguide material leading toextremely high sensitivity. Some biosensor systems based on Ta2O5 waveguides alreadytook the step into commercialization. This report reviews the various detection systems interms of limit of detection, the applications, and the suitable surface chemistry.

[Mobility and balance]. / Mobilität und Balance.

Quality of life is strongly associated with the mobility of elderly people. Falls often cause restricted mobility, a decline in activities of daily living and an increased risk of institutionalisation. Frailty, commonly associated with aging, is a biologic syndrome of decreased resistance to stressors, resulting from declines across multiple physiological systems. Changes in mobility and gait constitute part of the frailty syndrome. Since more than one third of persons over the age of 65 fall each year, prevention of falls is very important. Already while taking the patients' history special emphasis should be laid on matters associated with an increased risk of falling, such as the use of more than four medications. To assess mobility several brief tests exist (i.e. Timed up & go [17], Walking while Talking [20]) which immediately yield information regarding mobility and falling risk. Patients with poor performance on such tests or those with a history of several falls should undergo a spatio-temporal gait analysis in order to determine a possible cause as well as suitable interventions. Additionally, the objective measurement of temporo-spatial gait parameters under dual task conditions may detect deficits in cognitive function. Several interventions have been shown to have favourable effects on gait stability and the occurrence of falls. Proprioceptive problems can be partially compensated for by wearing special shoes. Also, different movement exercises such as Tai Chi Chuan, Jaques-Dalcroze eurhythmics and social dancing are associated with better balance and gait safety, and a reduction of falls.

[Modern intensive care]. / Moderne Intensivmedizin.

Frailty associated functional changes in the elderly lead to different problems treating geriatric patients in an intensive care unit. Patients suffering from frailty have less physiological reserves in acute illness, complications are more frequent and recovery is clearly delayed. Frailty is also an established and independent predictor for mortality. Therefore understanding of physiological ageing and knowledge of geriatric syndromes must be part of modern intensive care medicine. The importance of Frailty for intensive care is shown by means of selected clinical pattern.