An under recognized cause of preventable mortality is healthcare-associated (nosocomial) infections such as biofilms found on implants and catheters. About 5% of U.S. and E.U. patients acquire nosocomial infections leading to prolonged hospitalization, increased patient suffering, and mortality rates. To date, no satisfactory solutions are available to monitor biofilm formation under near-native conditions. As a consequence, in the present work, we report the development of a disposable microfluidic biochip capable of continuously monitoring cell population dynamics under physiological shear force conditions. We demonstrate the simultaneous application of contactless bioimpedance spectroscopy and amperometric measurements to monitor fungal biofilm growth rates and metabolic activities. Quantitative cell analysis is accomplished by the use of high-density interdigitated capacitors (microIDC) isolated by a 700 nm epoxy (SU-8 resist) based passivation layer to noninvasively assess biofilm formation in predefined proliferation chambers. Additionally, biofilm respiration activity is measured using redox-mediators oxidized at band electrodes located downstream within microchannels. The disposable biofilm analysis platform is used to continuously monitor the dynamic responses of C. albicans to different glucose and galactose concentrations.
Rapid detection of viral contamination remains a pressing issue in various fields related to human health including clinical diagnostics, the monitoring of food-borne pathogens, the detection of biological warfare agents as well as in viral clearance studies for biopharmaceutical products. The majority of currently available assays for virus detection are expensive, time-consuming, and labor-intensive. In the present work we report the creation of a novel micro total analysis system (microTAS) capable of continuously monitoring viral contamination with high sensitivity and selectivity. The specific interaction between shape and surface chemistry between molecular imprinted polymer (MIP) and virus resulted in the elimination of non-specific interaction in the present sensor configuration. The additional integration of the blank (non-imprinted) polymer further allowed for the identification of non-specific adsorption events. The novel combination of microfluidics containing integrated native polymer and MIP with contact-less dielectric microsensors is evaluated using the Tobacco Mosaic Virus (TMV) and the Human Rhinovirus serotype 2 (HRV2). Results show that viral binding and dissociation events can be readily detected using contact-less bioimpedance spectroscopy optimized for specific frequencies. In the present study optimum sensor performance was achieved at 203 kHz within the applied frequency range of 5-500 kHz. Complete removal of the virus from the MIP and device reusability is successfully demonstrated following a 50-fold increase in fluid velocity. Evaluation of the microfluidic biochip revealed that microchip technology is ideally suited to detect a broader range of viral contaminations with high sensitivity by selectively adjusting microfluidic conditions, sensor geometries and choice of MIP polymeric material.