ON-CHIP MICRODIALYSIS SYSTEM WITH FLOW-THROUGH GLUCOSE SENSING CAPABILITIES

Open Access
- Author:
- Hsieh, Yi-Cheng
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- July 28, 2006
- Committee Members:
- Jeffrey D Zahn, Committee Chair/Co-Chair
Arnold Anthony Fontaine, Committee Member
Nadine B Smith, Committee Member
Michael V Pishko, Committee Member - Keywords:
- microfluidics
glucose sensing
microdialysis
impedance sensing - Abstract:
- Microdialysis is a sampling technique based on controlling the mass transfer rate of different-sized molecules across a semipermeable membrane. Since the dialysis process does not change or affect the surrounding fluid, it is viewed as a tool for continuous monitoring of human metabolites for diabetes treatment. In diabetes treatment, microdialysis probes have been used as sampling systems coupled to a glucose biosensor but struggle to obtain high recoveries of analytes while the sampling housing, probes, and glucose sensors are fabricated as separate pieces and then assembled resulting in a large dead volume. An in-situ combination of a miniaturized microdialysis probe with an integrated glucose sensor allows both a high glucose recovery and frequent glucose sampling for continuous patient monitoring. A microdialysis chip with flow-through electrochemical glucose sensing capabilities is presented here. The system was fabricated by bonding a 6 um thick polycarbonate track-etch membrane with varying pore sizes onto microfluidic channels with the sensing electrodes patterned within the microchannels. A complete fabrication protocol for this device was developed with a non-leaking and reproducible bond between the microfluidic channels and the membrane. The integrated sampling and sensing components were both based on the same thin-film fabrication methods, which can reduce the dead volume and enhance microdialysis recovery with better time resolution. As the first step toward the on-chip integration of a microdialysis system and a glucose sensor, impedance electrodes sputtered within the microchannels were used to characterize conductivity of a dialyzed phosphate buffered saline (PBS) solution, which is a function of PBS concentration. The permeability of the membrane to the salt ions was obtained as 0.246 um/s (15 nm diameter pores). Subsequently, experiments measuring PBS dialysis in the time-domain at 64.4% recovery were conducted. Next glucose microdialysis with continuous sensing was demonstrated, the permeability of glucose to the polycarbonate membrane with 100 nm diameter pore size was obtained to be 5.44 um/s. Glucose recovery of 99% was observed using this microdialysis system at a perfusion flow rate of 0.5 ul/min. Experiments monitoring glucose concentration in the time-domain were also performed. The electrochemical sensing component was able to continuously track concentration changes in the reservoir. This system is expected to have the proper sensitivity to track physiologically relevant concentration changes of glucose (maximum change rate ~4 mg/dl-min with periodicity of 1 hour or greater) with minimal lag time and amplitude reduction for continuous glucose monitoring for diabetes treatment.