Study On Interstitial Fluid Transdermal Extraction Method And System Based On PDMS Microfluidic Chip

The continuous glucose monitoring technology based on transdermally extracted interstitial fluid (ISF) is a hot research topic, because it offers promise of minimally invasive, continuous, and real-time glucose monitoring. But the tiny volume of the transdermally extracted ISF makes the transdermal extraction, collection, transport, volumetric measurement and glucose concentration measurement of the ISF very difficult. The microfluidic chip technology is essential to realize the miniaturization and integration of the function modules for ISF transdermal extraction, collection and volumetric measurement, build the devices for studying the scientific issues and key technologies of the continuous glucose monitoring technology, and promote the practical and clinical applications of the continuous glucose monitoring instruments based on transdermally extracted ISF. Therefore, the microfluidic chip technology is utilized to study on the method of ISF transdermal extraction. And a chip level system for ISF transdermal extraction is developed. Furthermore, the key technical issues in transdermal ISF extraction, collection and volumetric measurement are studied and solved with the chip level system.A Venturi tube fabricated with Polydimethylsiloxane (PDMS) is proposed. According to the fluid mechanics theory, the influence of the Venturi structure on the relation between output vacuum and input pressure is analyzed. And the analysis results and the classical standards are validated by the experimental results. The methods for Venturi structure optimization are concluded, and the optimized Venturi structure which satisfies the requirements of transdermal ISF extraction and fluid transport in the microchannels is presented.A micro volume sensor of conductive liquid is proposed. The properties of the micro volume sensor with two electrode pairs are studied by measuring the volume of conductive liquid which flows with uniform velocity or uniform acceleration. Based on the analysis of the factors that affect the accuracy, stability and miniaturization of the micro volume sensor with two electrode pairs, a micro volume sensor with four electrode pairs and a particular curve microchannel is proposed. The micro volume sensor with four electrode pairs is tested for controlling the defined volume normal saline injection and measuring the micro volume of conductive liquid. The experimental results show that the micro volume sensor with four electrode pairs stably (coefficient of variation is 0.0041, n=20) controls 9.70μL normal saline injections, and accurately measures the volume of normal saline. The absolute error of 0-3μL normal saline volume measurement is less than 0.17μL. Especially, when the normal saline volume is no more than 1.50μL, the absolute error is less than 0.04μL.A pneumatic valve is proposed for controlling the fluid flow in the microchannels. It is designed and fabricated based on the low elastic modulus and high flexibility properties of PDMS. The close pressures of the pneumatic valve under different vacuum are tested, and they are about 60 kPa which is close to the theoretical derivation result (62.85 kPa). In the microchannel, the flow of normal saline induced by 95 kPa vacuum is controlled properly by the pressure, switching between 170 kPa and the atmospheric pressure, on the top of the pneumatic valve membrane.A structure of the system which integrates the Venturi tube, micro volume sensor, pneumatic valves, chambers and microchannels together is proposed. Five PDMS layers are bonded together utilizing the oxygen plasma bonding technique to realize the integration of these core components. A simulating experiment of transdermal ISF extraction, collection and volume measurement with full-thickness pig skin is performed using the integrated system. In the experiment, the system continuously and automatically realizes the functions of defined volume normal saline injection, normal saline (with different glucose concentrations) extraction through low frequency ultrasound pretreated pig skin, lossless collection of the sample solution, and accurately volume measurement of the transdermally extracted normal saline with different glucose concentrations. The absolute error of the volume measurement is less than 0.05μL, and it achieves the target of enhancing the prediction accuracy of glucose concentration in ISF.