Simulation based characterization of transport phenomena and affinity reactions at the solid phase in centrifugal microfluidics

• Applicant: Professor Dr.-Ing. Nils Paust
• Subject Area: Microsystems
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286516335

Highly sensitive analysis is required for the point of care (PoC) to enable rapid diagnostics and timely treatment. A short assay time is in particular important. However, to provide economically reasonable and highly sensitive analysis under PoC conditions (small compact devices, variable ambient conditions) is extremely challenging.Centrifugal microfluidics has the potential to automate PoC tests for small analyte concentrations (< 10pg/ml). Scalable volume forces in the centrifugal gravity field enable robust automation of fluidic operations, widely independent from variable sample matrixes (viscosity and wetting properties) and ambient conditions (temperature, pressure, humidity, etc.). All important processes are controlled by the rotational frequency of the rotor, only. Interfaces of the testchips are simple because no tubing or pumps are required.PoC tests (immuno- and molecular diagnostic) are typically based on affinity reactions that separate the analyte from the sample matrix for subsequent quantification. To keep the analysis time small and reach high sensitivity, the transport of analyte to the functionalized solid phase and the removal of non-affine substances has to be very efficient. However, the state of the art does not provide fundamental knowledge of transport phenomena in centrifugal microfluidics. The impact of the interplay of inertia forces (centrifugal-, Euler- and Coriolis force) on flow profiles and resulting transport of analyte to the solid phase remains unresolved. Consequently, highly sensitive PoC tests based on centrifugal microfluidics have not been demonstrated so far. The goal of this project is to establish fundamental knowledge of centrifugal microfluidic transport phenomena and analyte transport for affinity reactions. The impact of varying ambient conditions and sample matrixes on binding efficiency and speed should be evaluated. Based on this knowledge highly sensitive PoC tests will be automated with centrifugal microfluidics.This project aims to achieve the following sub-goals:Establish models of convective and diffusive transport of analyte and analyte-conjugate-complexes and of binding of analytes to solid phases in centrifugal microfluidic reaction chambers.Develop experiments for model validation.Demonstration of simulation based layout by implementing a highly sensitive Troponin assay (detection limit < 3pg/ml; <10% CV at 10 pg/ml). Validation with clinical samples.Establish a component library for the design of centrifugal microfluidic PoC tests.

• DFG Programme: Research Grants