A Continuous Glucose Monitoring Chip System Based On Interstitial Fluid Transdermal Extraction

In order to realize the transdermal extraction, collection, volumetric measurementand glucose concentration measurement of the micro-volume interstitial fluid (ISF),two major problems need to be solved: lossless collection of transdermally extractedISF and concentration detection of the sample solution. A chip level system forcontinuous glucose detection based on the ISF transdermal extraction is developed inthis thesis. This system is composed of an ISF transdermal extraction chip and amicro-glucose sensor. In this dissertation, we are working on key technical issues intransdermal ISF extraction, lossless collection, volumetric measurement and theconcentration detection process.Several key issues in this chip level system have been studied. The main worksinclude:(1) The parameters of the micro vacuum generator of the ISF transdermalextraction chip are optimized to obtain a lower output vacuum under the low inputpressure. And the extraction chamber is adjusted, so the sealing characteristic betweenthe chip and the skin is improved. We add another two electrode pairs to the chip torealize the automatic control of sample solution in the collection process(2) A micro positive pressure generator based on the gas production in thermaldecomposition of azobisisobutyronitrile (AIBN) is presented. Experimental resultsshow that positive pressures needed in the system can be obtained by adjusting theheating current and the quality of the AIBN.(3) A simple fabrication process is employed to complete the ISF transdermalextraction chip which contains five layers as follows: micro positive pressuregenerator layer, micro-pneumatic valve layer, micro-channels layer, micro-electrodelayer and micro chamber layer was fabricated by this process with PDMS. These fivePDMS layers are integrated utilizing the corona bonding technique.(4) The principle, design and fabrication process of the micro affinity glucosesensor together with the micro-fiber SPR glucose sensor are analyzed. The integrationdesign of the ISF transdermal extraction chip with the above two micro glucosesensor is completed. (5) A system prototype which integrates the ISF transdermal extraction chip andthe micro glucose sensor is completed. A series of experiments include pre-injection,quantitatively normal saline injection and the simulating tissue fluid transdermalextraction are performed on this integrated system. The experimental results show thatthe micro volume sensor with four electrode pairs stably controls the9.50μL normalsaline injections (coefficient of variation is0.005, n=20), and accurately measures thevolume of normal saline. The absolute error of the0-2μL normal saline volumemeasurement is less than0.05μL.