Integrated sampling-and-sensing using microdialysis and biosensing by particle motion for continuous cortisol monitoring

Abstract

Microdialysis catheters are small probes that allow sampling from biological systems and human subjects with minimal perturbation. Traditionally, microdialysis samples are collected in vials, transported to a laboratory, and analysed with typical turnaround times of hours to days. To realize a continuous sampling-and-sensing methodology with minimal time delay, we studied the integration of microdialysis sampling with a sensor for continuous biomolecular monitoring based on Biosensing by Particle Motion (BPM). A microfluidic flow cell was designed with a volume of 12 μl in order to be compatible with flowrates of microdialysis sampling. The analyte recovery and the time characteristics of the sampling-and-sensing system were studied using a food colorant in buffer and using cortisol in buffer and in blood plasma. Concentration step functions were applied, and the system response was measured using optical absorption and a continuous BPM cortisol sensor. The cortisol recovery was around 80% for a 30 mm microdialysis membrane with a 20 kDa molecular weight cut-off and a flowrate of 2 μl min⁻¹. The concentration-time data could be fitted with a transport delay time and single-exponential relaxation curves. The total delay time of the sampling-and-sensing methodology was about 15 minutes. Continuous sampling-and-sensing was demonstrated over a period of 5 hours. These results represent an important step toward integrated sampling-and-sensing for the continuous monitoring of a wide variety of low-concentration biomolecular substances for applications in biological and biomedical research.