Smartphones are developing into all-purposes devices. In the present work, the employment/application of smartphones as medical devices in home care and point-of-care (POC) diagnostics are investigated in the analysis of Lateral Flow Assays (LFA). A smartphone-based LFA reader was developed for the quantitative analysis of D-Dimer – a biomarker indicating e.g. thrombotic event or danger of embolism.The proof-of-concept has been shown with multiple smartphones in establishing: (I) Optimal dimensions of the LFA cell of 72.11mm distance of smartphone to D-Dimer test leading to a coefficients of variances (CV) between 0.8% and 4.2%. (II) Inter-device investigations: CVs around 13.5%; a limit of detection (LOD) of 100ng/ml (DDU) D-Dimer. (III) Inter-smartphone investigations: CV about 16%, a limit of detection (LOD) at 66.4ng/ml (DDU). (IV) Calibrations: CV and LOD of three smartphones are comparable to the commercial available LFA reader. Further development to put the multiple smartphone-based LFA reader on the market.
Conventional Bioreactor systems for cultivating cells in Life Science have been widely used for decades. An in vitro cell cultivation bioreactor should reliably and reproducibly mimic the in vivo microenvironment of the cultured cells. Normally, mammalian cell cultures are performed in conventional bioreactor devices such as culture flasks and culture-dishes. However, these tools have fundamental limitations due to being inappropriate for high throughput screening and consume a considerable amount of resources and time [1]. Therefore, there is a trend towards miniaturization, disposables and even micro platforms that fulfill increasing demands strongly aiming for production and testing of novel pharmaceutical products. Here we present the development and manufacture of a disposable miniaturized flow-through bioreactor system that can be produced in large numbers at low costs. nanoporous hollow fibers are located at the fluidic sources and drains of the miniaturized bioreactors and retain cells. The necessary mixture of oxygen and carbon dioxide is provided via diffusion through a semi-permeable membrane. Fluidic connections allow the continuous feeding of the cells adding nutrient solution at constant rates at the inlet of the micro bioreactor and removing the solution at the same rate at the outlet. This medium can be collected and used for subsequent analysis. Different designs and concepts for such bioreactors were carried out with varying numbers of plates, and integrated or joined miniaturized reactor chambers. First tests show full technical and biological functionality, cells could successfully be cultivated at high viability rates for some days.
The objective of the present work was the development of a micro-pH meter for the determination of the pH value within bioreactors with a volume of up to 200 μl in total. Two different prototypes of optodes were designed and tested. In a first approach spectroscopic analysis of bromothymol blue in a micro-sized-channel structure was carried out utilizing glass fibers, enabling measurements in sample volumes down to the range of picoliters. In a second approach a different illumination system consisting of a RGB-sensor and a LED light source was used. Phenol red was successfully applied as the pH indicator for this setup.
A bioreactor is a device simulating physiological environments for different biotechnological applications. In highly promising research fields like tissue engineering micro-sized bioreactors were utilized successfully promoting mammalian cells to grow and build 3D cell structures similar to in vivo environments. For any practical application and even for improved R&D it is necessary to generate and maintain a physiological environment over the whole cultivation period (hours, days or weeks, in case of artificial organs even up to months). Depending on the field of application physiological environments can comprise different parameters. In case of mammalian cell lines these parameters require a complex supply and monitoring system. Thus, we developed a semi-automated bioreactor-system for long-term cultivation of different mammalian cell types imitating physiological conditions. The system included detection and control of the following parameters: temperature, pH-value, gas concentration and the continuous supply with nutrients. A micro fluidic network was established enabling a high through-put cultivating system as bioreactor-system. The bioreactor-system consists of several micro-sized chambers in a microliter scale (the related article discussing the micro-sized chambers “Miniaturized Flow-Through Bioreactor for Processing and Testing in Pharmacology” by Boehme et al is published within this issue). The chambers were placed in a polymeric slide each with an individual medium supply and disposal. Every single chamber thus was connected to an individual syringe-based micro-pump setup and supplied by nutrients solution with a velocity of 100μl/h. The pH-value was observed optically and controlled via CO2 supply. All gas interchanges into every single chamber were realized via semi permeable membranes. The required temperature was adjusted via an appropriate custom-fit heating system utilizing MOSFETs allocated on an aluminum board along the slides. Two slides each were housed in a PMMA case. This bioreactor-system is a first prototype for larger systems aiming for the parallel operation of up to 100 micro-sized reaction chambers.
This work presents a photolithographic rapid prototyping process for producing thin films ("Rapid Phototyping"). This process allows a quick and cost-effective generation of scalable thermopile microstructures using commercial equipment and materials. Structural widths of 100x250μm can be produced reproducible in a lift-off process with an accuracy of 5 microns vertically and 30 microns horizontally.
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