23 research outputs found
Reversible low-light induced photoswitching of crowned spiropyran-DO3A complexed with gadolinium(III) ions.
Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A, which improves its solubility in dipolar and polar media and stabilizes the merocyanine isomer. Adding the lanthanide ion gadolinium(III) to the macrocyclic ring system leads to a photoresponsive magnetic resonance imaging contrast agent that displays an increased spin-lattice relaxation time (Tâ) upon visible light stimulation. In this work, the photoresponse of this photochromic molecule to weak light illumination using blue and green light emitting diodes was investigated, simulating the emission spectra from bioluminescent enzymes. Photon emission rate of the light emitting diodes was changed, from 1.75 Ă 10Âčⶠphotons·sâ»Âč to 2.37 Ă 10ÂčÂČ photons·sâ»Âč. We observed a consistent visible light-induced isomerization of the merocyanine to the spiropyran form with photon fluxes as low as 2.37 Ă 10ÂčÂČ photons·sâ»Âč resulting in a relaxivity change of the compound. This demonstrates the potential for use of the described imaging probes in low light level applications such as sensing bioluminescence enzyme activity. The isomerization behavior of gadolinium(III)-ion complexed and non-complexed spiropyran-DO3A was analyzed in water and ethanol solution in response to low light illumination and compared to the emitted photon emission rate from over-expressed Gaussia princeps luciferase
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Adhesion and relaxation of a soft elastomer on surfaces with skin like roughness
For designing new skin adhesives, the complex mechanical interaction of soft elastomers with surfaces of various roughnesses needs to be better understood. We systematically studied the effects of a wide set of roughnesscharacteristics, film thickness, hold time and material relaxation on the adhesive behaviour of the silicone
elastomer SSA 7â9800 (Dow Corning). As model surfaces, we used epoxy replicas obtained from substrates with roughness ranging from very smooth to skin-like. Our results demonstrate that films of thin and intermediate thickness (60 and 160 ÎŒm) adhered best to a sub-micron rough surface, with a pull-off stress of about 50 kPa. Significant variations in pull-off stress and detachment mechanism with roughness and hold time were found. In contrast, 320 ÎŒm thick films adhered with lower pull-off
stress of about 17 kPa, but were less sensitive to roughness and hold time. It is demonstrated that the adhesion performance of the siliconefilms to rough surfaces can be tuned by tailoring the film thickness and contact time
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Adhesion and Cellular Compatibility of Silicone-Based Skin Adhesives
Pressure-sensitive adhesives based on silicone materials have emerging potential as adhesives in healthcare products, in particular for gentle skin adhesives. To this end, adhesion to rough skin and biocompatibility are crucial factors for a successful implementation. In this study, the mechanical, adhesive, and biological properties of the two-component poly(dimethylsiloxane) Soft Skin Adhesive MG 7-9800 (SSA, Dow Corning) have been investigated and compared to Sylgard 184. Different mixing ratios of SSA's components allow for tuning of the shear modulus, thereby modifying the adhesive properties of the polymer. To give a comprehensive insight, the authors have analyzed the interplay between pull-off stress, adhesion energy, and stretch of the adhesive films on smooth and rough surfaces. The focus is placed on the effects of substrate roughness and on low pressure oxygen plasma treatment of the adhesive films. SSA shows superior biocompatibility in in vitro cell culture experiments. High pull-off stresses in the range of 3 N cmâ2 on a rough surface are achieved, promising broad application spectra for SSA-based healthcare products
Laboratory-Developed Tests: Design of a Regulatory Strategy in Compliance with the International State-of-the-Art and the Regulation (EU) 2017/746 (EU IVDR [In Vitro Diagnostic Medical Device Regulation])
Purpose: This study aimed at the development of a regulatory strategy for compliance of laboratory-developed tests (LDTs) with requirements of the Regulation (EU) 2017/746 (âEU-IVDRâ) under consideration of international requirements for LDTs as established in major regulatory regions. Furthermore, it was analysed in how far elements of current LDT regulation could qualify for an internationally harmonised concept ensuring quality, safety and performance of LDTs. Methods: A review of regulatory literature including legislation as well as guidance documents was performed. The regulatory strategy was adapted from international guidance concepts used for commercially marketed IVD. It was then applied to the example of a large medical laboratory in the EU. A high-level comparison was conducted to identify gaps and matches between the different international regulatory requirements for LDTs. Results: A four-step strategy for compliance of LDTs with the EU IVDR was implemented in an exemplary medical laboratory. On the basis of an internationally used LDT definition, LDTs constitute nearly 50% of the total IVD devices used in the laboratory. While an ISO 15189-compliant QMS is a major component, it should be accompanied by the application of appropriate processes for risk management, performance evaluation and continuous monitoring of LDTs. At least six criteria represent common characteristics of a potential, internationally convergent concept for the regulation/standardization of LDTs. Conclusions: This study confirms the impact of LDTs for individualized and innovative medical laboratory testing. Prerequisites for LDT use as especially given by the IVDR and missing interpretation in the EU with regard to the scope of LDT definition, the application of standards and the extent of documentation for LDTs currently lead to uncertainties for both laboratories and regulatory bodies responsible for LDT oversight. The characteristics identified as common criteria for ensuring quality, safety and performance of LDTs may be considered as central elements of future international consensus guidance. © 2021, The Author(s)
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Like a Second Skin: Understanding How Epidermal Devices Affect Human Tactile Perception
The emerging class of epidermal devices opens up new opportunities for skin-based sensing, computing, and interaction. Future design of these devices requires an understanding of how skin-worn devices affect the natural tactile perception. In this study, we approach this research challenge by proposing a novel classification system for epidermal devices based on flexural rigidity and by testing advanced adhesive materials, including tattoo paper and thin films of poly (dimethylsiloxane) (PDMS). We report on the results of three psychophysical experiments that investigated the effect of epidermal devices of different rigidity on passive and active tactile perception. We analyzed human tactile sensitivity thresholds, two-point discrimination thresholds, and roughness discrimination abilities on three different body locations (fingertip, hand, forearm). Generally, a correlation was found between device rigidity and tactile sensitivity thresholds as well as roughness discrimination ability. Surprisingly, thin epidermal devices based on PDMS with a hundred times the rigidity of commonly used tattoo paper resulted in comparable levels of tactile acuity. The material offers the benefit of increased robustness against wear and the option to re-use the device. Based on our findings, we derive design recommendations for epidermal devices that combine tactile perception with device robustness
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A Self-Adhesive Elastomeric Wound Scaffold for Sensitive Adhesion to Tissue
Pressure sensitive adhesives based on silicone materials are used particularly for skin adhesion, e.g., the fixation of electrocardiogram (ECG) electrodes or wound dressings. However, adhesion to sensitive tissue structures is not sufficiently addressed due to the risk of damage or rupture. We propose an approach in which a poly-(dimethylsiloxane) (PDMS)-based soft skin adhesive (SSA) acts as cellular scaffold for wound healing. Due to the intrinsically low surface free energy of silicone elastomers, functionalization strategies are needed to promote the attachment and spreading of eukaryotic cells. In the present work, the effect of physical adsorption of three different proteins on the adhesive properties of the soft skin adhesive was investigated. Fibronectin adsorption slightly affects adhesion but significantly improves the cellular interaction of L929 murine fibroblasts with the polymeric surface. Composite films were successfully attached to explanted tympanic membranes. This demonstrates the potential of protein functionalized SSA to act as an adhesive scaffold in delicate biomedical applications
Development of a Three-Dimensional In Vitro Model for Longitudinal Observation of Cell Behavior: Monitoring by Magnetic Resonance Imaging and Optical Imaging
Purpose: The aim of this study is the development of a three-dimensional multicellular spheroid cell culture model for the longitudinal comparative and large-scale screening of cancer cell proliferation with noninvasive molecular imaging techniques under controlled and quantifiable conditions. Procedures: The human glioblastoma cell line Gli36ÎEGFR was genetically modified to constitutively express the fluorescence protein mCherry, and additionally labeled with iron oxide nanoparticles for high-field MRI detection. The proliferation of aggregates was longitudinally monitored with fluorescence imaging and correlated with aggregate size by light microscopy, while MRI measurements served localization in 3D space. Irradiation with Îł-rays was used to detect proliferational response. Results: Cell proliferation in the stationary three-dimensonal model can be observed over days with high accuracy. A linear relationship of fluorescence intensity with cell aggregate size was found, allowing absolute quantitation of cells in a wide range of cell amounts. Glioblastoma cells showed pronounced suppression of proliferation for several days following high-dose Îł-irradiation. Conclusions: Through the combination of two-dimensional optical imaging and 3D MRI, the position of individual cell aggregates and their corresponding light emission can be detected. This allows an exact quantification of cell proliferation, with a focus on very small cell amounts (below 100 cells) using high resolution noninvasive techniques as a well-controlled basis for further cell transplantation studies
Reversible low-light induced photoswitching of crowned spiropyran-DO3A complexed with gadolinium(III) ions.
Molekulare Markierungsstrategien fĂŒr die optische und magnetresonanztomographische zellulĂ€re Visualisierung
Cellular labelling for molecular and multimodal visualisation was designed and validated. Of interest was the connection of optical detection and magnetic resonance imaging to combine quantitative with three dimensional information. Detection and quantification of cell amounts below 1000 cells were focused. Enhanced fluorescence proteins were overexpressed for optical imaging and for bioluminescence imaging firefly luciferase was used. A fluorescence protein with a longer emission wavelength was used to enable further efficient in vivo studies. Cells were labeled with superparamagnetic iron oxide particles for the MRI detection and uptake and distribution of the particles was investigated. For enhanced labeling of cells a liposomal based strategy was implemented and modified. Overexpression of human heavy chain ferritin in combination with firefly luciferase in glioma cells led to a cell specific internal MR contrast in combination with bioluminescence detection. For efficient transduction a lentiviral system was used. Exchange of promoters is promising for cell or tissue specific expression. Another strategy was the overexpression of artifical surface receptors which were truncated at cytoplasmic site to avoid further signal protein interaction. Iron oxide particles, conjugated to antibodies enabled MRI localisation after antibody receptor binding. This extracellular labeling was determined for tumour cells and neural cells. Neural cells were differentiated from embryonic stem cells with modified and optimized protocols