(6eu) Numerical Simulation based Design of Point of Care Diagnostic Devices

Teaching Interests: Fluid Mechanics, Heat Transfer, Numerical methods for chemical engineers

DNA amplification refers to the production of multiple copies of a DNA sequence from a single copy. Polymerase chain reaction or PCR has been the regular choice for scientists in order to carry out DNA amplification reaction. However, the recent invention of the loop-mediated isothermal amplification (LAMP) method, a decade ago has given new impetus towards the development of point of care diagnostic tests based on amplification of DNA. In the recent past, LAMP has been carried out using various microfluidic technologies. The manufacturing of these devices is rigorous and expensive. Paper membranes have tremendous potentiality in replacing the existing technology as the manufacturing cost of a paper-based device is comparatively lesser and a paper based DNA amplification device would be relatively easy-to-use. However, this emerging technology is yet to be explored in details. The current work presents an insight into the CFD simulations for LAMP amplification reaction on a porous membrane. In addition, a mathematical model for LAMP amplification reaction was derived for the first time. The logistic equation and Richard's curve model were found to be the best fits. However, due to the significantly higher correlation coefficient for logistic equation, it was used in the simulation studies. The porous membrane used in the current work is a Nitrocellulose membrane (pore size values varied from 14.5 µm to 0.45 µm). Nitrocellulose membrane with a pore size of 0.45 µm is suitable for most protein blotting applications. Our major aim is to enhance the number of DNA copies via LAMP on the paper membrane. The mathematical model considered is a convection-diffusion-reaction model and the problem was solved using Finite Element method via COMSOL Multiphysics 5.0. The element size (e) varied between 2.4×10^-4 (min) - 0.12 (max) and the maximum element growth rate was taken as 1.1. Triangular meshes were chosen for the entire domain except the boundaries (both the horizontal walls and the outlet) where boundary layers with a thickness adjustment factor of 0.5, were implemented. Results are demonstrated in terms of DNA amplicon production for various pore sizes (Ɛ), aspect ratio of the geometry (A) and inlet concentration of the amplicons. Based on these simulations, a near optimal design was achieved based on the maximum production of DNA copies.