Continuous Microfluidic Viscometers for Biochemical and Diagnostic Analysis

[摘要] Microfluidic technologies have advanced rapidly over the past two decades. Numerous microfluidic devices to assess different biomarkers have been reported, yet very few address physical properties, such as viscosities, of biological specimens. Continuous monitoring of viscosity changes provides a new biological and diagnostic parameter not yet made readily accessible due to the low obtainable volume of many biological specimens. In this dissertation, we have developed a droplet-based, water-in-oil continuous viscometer capable of measuring viscosity changes in 10 seconds or less and consuming a total sample volume of less than 1 microliter per hour.The viscometer employs a flow-focusing geometry and generates droplets under constant pressure. The length of the droplets is highly correlated to the aqueous-phase viscosity at high ratios of aqueous-to-oil inlet pressure, resulting in a linear calibration relationship for viscosity measurements. Theoretical analysis verifies the linear relationship and guides viscometer optimization. The viscometer can be used for Newtonian fluids and, by accurately calculating shear rates, for non-Newtonian fluids. The shear rates can be adjusted experimentally by varying the input pressures. The viscometer measures viscosities reliably over three orders of magnitude with less than 5% error. Using the viscometer, we measured viscosity changes of whole blood during blood coagulation continuously under different conditions.We have also developed a particle-based microviscometer for label-free DNA detection by applying the asynchronous magnetic bead rotation (AMBR) phenomenon. We have demonstrated experimentally that the rotation period of paramagnetic beads is linearly proportional to the viscosity of a DNA solution surrounding the paramagnetic beads, as expected theoretically. Simple optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of DNA concentration or average fragment length. The effects of different operating conditions have been investigated and a standard deviation of less than 10% has been achieved for viscosity measurements under the optimal conditions. The response of the AMBR viscometer yields reproducible measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at template concentrations across a 5000-fold range. Preliminary design and operation of a ChessTrap device has been demonstrated to trap single particles into individual chambers for viscometer automation.

[发布机构] University of Michigan

[效力级别] Rheology

[关键词] Viscometer;Rheology;Microfluidics;Point-of-care devices;Biomedical Engineering;Chemical Engineering;Engineering (General);Science (General);Engineering;Health Sciences;Science;Chemical Engineering