Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in ‘organ-on-a-chip’ devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in ‘human-on-a-chip’ systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and microsystems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in ‘human-on-a-chip’ systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.
The development of a surface plasmon resonance (SPR) spectrometer comprising angular-resolved analysis for quasi-monochromatic illumination is reported. The optical system utilizes disposable, injection-molded chips combined with a lateral imaging optical system for parallel analysis of one-dimensional spot arrays. Further parallelization is achieved by introducing a segmented light source. This source sequentially illuminates three neighbored one-dimensional arrays in order to keep angular-resolved analysis without introducing any mechanically moving parts. This system is applied to detect genetic variations among different DNA samples obtained from polymerase chain reaction (PCR). For this purpose, 135 spots on the chip surface have been prepared by spotting and analyzed separately
Aptamers are synthetic single-stranded oligonucleotides which bind specifically to their target. They offer several advantages over antibodies. For example, aptamers can be produced under unphysiological conditions against almost any target, including toxic or pathological substances. They are also quicker and cheaper produced than antibodies, and are easy to modify without loss of activity. Furthermore, they exhibit high stability under a width range of conditions. Consequently, they make excellent receptors for the use in biosensors. This article describes the evaluation of a novel aptasensor based on the Surface Plasmon Resonance (SPR)-system developed by the Fraunhofer Institute for Applied Optics and Precision Engineering IOF (Jena, Germany) using a thrombin–aptamer interaction as a model system. The biotin-tagged aptamer was attached to the sensor's gold surface by means of its interaction with streptavidin. Thrombin solutions of different concentrations were pumped over this surface, and the interaction was measured under buffer flow. The binding signals for the thrombin–aptamer interaction were compared to those arising from a control random-oligonucleotide of the same size and bearing the same modifications. Using this approach, we were able to obtain reproducible, significant and stable signals with a limit of detection of about 26 nmol/L
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