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A spheroid-based biosensor for the label-free detection of drug-induced field potential alterations
(2012)
Using three-dimensional cell culture systems on Microelectrode arrays for biosensing applications
(2010)
Due to the increasing number of diabetes patients worldwide there is an enormous need for accurate, fast and someday also continuous or even closed loop monitoring of blood glucose level. More than 50 years after Clark and Lyons proposed the first glucose enzyme electrodes this concept is still widely in use today. Most concepts use the enzyme glucose oxidase (GOx) that reacts with glucose. These reactions cause a current that is proportional to the amount of glucose present at the sensor. Thus, if the sample volume is known, the blood sugar level can be measured. Although these electrodes have been in use for so long they have the disadvantage of a limited shelf time. In this work we present an enzyme free approach for glucose detection applying ultrathin gold films. According to the basic Fuchs-Sondheimer-theory and other more sophisticated models the resistivity of ultrathin metal films is dominated by scattering effects at their surface. Chemical reactions at the metallic surface are expected to change the conductivity properties and thus these changes can be used to detect molecules. This can be done by creating a self-assembled monolayer at the gold surface. When molecules such as glucose bind to the end groups of this layer the electron scattering and thus the conductivity of the film is expected to change. Ultrathin gold films with a thickness of 6 nm show the largest relative change in resistivity and are thus the preferred film thickness for this application. These gold films show a significant change in resistance when model molecules sodium sulfide and dextran are present, whereas the resistance of a platinum reference electrode does not change significantly.
In recent years, there has been an increasing interest in electrically conductive hydrogels for a wide range of biomedical applications, like tissue engineering or biosensors. In this study, we present a cost-effective conductive hydrogel based on alginate and graphene nanoplatelets for extrusion-based bioprinters. The hydrogel is prepared under ambient conditions avoiding high temperatures detrimental for cell culture environments. Investigation of the hydrogel revealed a conductivity of up to 7.5 S/cm, depending on the ratio of platelets. Furthermore, in vitro tests with human embyronic kidney cells - as an example cell type - showed good adhesion of the cells to the surface of the conductive hydrogel. Electrochemical measurements revealed a low electrode impedance which is desirable for the extracellular recording, but also low electrode capacitance, which is unfavorable for electrical stimulation purposes. Therefore, future experiments with the graphene nanoplatelets-based hydrogels will focus on electrodes for biosensors and extracellular recordings of neurons or cardiac myocytes.
A novel 3D-printed glucose sensor is presented for cell culture application. Glucose sensing was performed using a fluorescence resonance energy transfer (FRET)-based assay principle based on ConA and dextran. Both molecules are encapsulated in alginate microspheres and embedded in the UV-curable, stable hydrogel polyvinyl alcohol (PVA). The rheology of the formulation was adapted to obtain good properties for an extrusion-based printing process. The printed sensor structures were tested for their ability to detect glucose in vitro. A proportional increase in fluorescence intensity was observed in a concentration range of 0 - 2 g/L glucose. Tests with HEK cell cultures also showed good cell compatibility and excellent adhesion properties on plasma-treated Petri dishes. The printed sensors were able to detect the glucose decay associated with the metabolic activities of the fast-growing HEK cells in the cell culture medium over ten days. The proof-of-principle study shows that metabolic processes in cell cultures can be monitored with the new printed sensor using a standard fluorescence wide-field microscope.