On-chip microdialysis system with in-line sensing capabilities

Microdialysis probes have been used for diabetes treatment as continuous monitoring system coupled to a glucose sensor. An on-chip microdialysis system with in-line sensing electrodes is demonstrated. The response time of the microdialysis system was characterized and the permeability of the polycarbonate membrane (100nm pore size) to glucose was determined to be 2.53 μm/s (std:0.372 μm/s). As a first step towards greater biosensor integration with this miniaturized microdialysis system, a stacked system with in-line sensing electrodes was developed. Impedance electrodes within the microchannels were used to determine fluid resistance from a dialyzed phosphate buffered saline (PBS) solution, which characterizes solution conductivity as a function of PBS concentration. The permeability of the membrane to the salt ions was obtained as 0.74 μm/s (15 nm pores). Subsequently, experiments measuring PBS dialysis in the time-domain at 60% recovery were conducted. The PBS concentration of the reservoir was changed in either a step response or sinusoidally with an 800 second period. The subsequently measured impedance indicates that the system is able to continuously track concentration changes in the reservoir with a 180 second system response delay. Most of this delay is due to the dead volume within the tubing between the syringe pumps and the microsystem In addition the predicted response was modeled using linear systems theory and matches the experimental measurements. This system is expected to have the proper sensitivity to track physiologically relevant concentration changes of biomolecules such as glucose (which has a physiological maximum change rate of ∼4mg/dL-min with a periodicity of 1 hour or greater) with minimal lag time and amplitude reduction.