טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentRosenfeld Tally
SubjectEnhancing the Sensitivity and Functionality of Paper-Based
Devices by Isotachophroesis and Electrosmotic
Flow
DepartmentDepartment of Mechanical Engineering
Supervisor Professor Moran Bercovici
Full Thesis textFull thesis text - English Version


Abstract

Microfluidic paper-based analytical devices (also known as ‘µPADs‘) have gained significant attention in recent years due to their potential as a low-cost, durable, and simple to use diagnostic platform. The most common use of paper-based tests to date is in lateral flow tests (LFT), such as malaria detection, and home pregnancy tests. However, despite well identified biomarkers, many diagnostic needs cannot be met by the current sensitivity of such tests.

This dissertation is concerned with modeling of ITP focusing and electroosmotic pumping in paper-based devices, and their application toward increasing the sensitivity and functionality of low-cost diagnostic devices.

In the first part of the dissertation, we present the development, formulation, and characterization of a novel paper-based device for Isotachophoresis (ITP) focusing. ITP is an electrophoresis technique capable of focusing sample ions of interest at a sharp electric field gradient formed at a very narrow interface between a high electrophoretic mobility leading electrolyte (LE) and a low electrophoretic mobility trailing electrolyte (TE). Using the ITP-enabled paper device, we have demonstrated the ability to focus sample of interest by as much as 1,000 fold in 6 minutes on μPAD. In addition, we introduce a novel analytical model for ITP sample accumulation in porous media, and identify a convenient figure of merit for assessing the efficiency of such devices. Furthermore, we present a model for heat transfer in such devices, which guided the design of the µPAD and its fabrication process.

In the second part, we present the development and formulation of another novel paper-based device which utilizes the native high electroosmotic flow (EOF) in nitrocellulose to achieve stationary ITP focusing. We provide a brief theory for EOF-balanced ITP focusing under continuous injection from a depleting reservoir and present the design of a short (7 mm) paper-based microfluidic channel, which allows a 200 μL sample to be processed in approximately 6 min, resulting in a 20,000-fold increase in concentration - a full order of magnitude improvement compared to previous paper-based ITP devices.

In the third part, we leverage this fundamental work and demonstrate the ability of ITP to accelerate biological surface and bulk reactions for the sensitive detection of nucleic acids. Furthermore, we utilize the small footprint of the channel and show a multiplexed platform in which 12 assays operate in parallel in a 24-well plate format. Finally, we present the integration of the technique into a self-contained hand-held device.

μPADs rely on capillary flow to achieve filling, mixing and delivery of liquids, and liquid flow within long porous paper channels is intrinsically slow. In the last part of the dissertation, we investigate the use of electroosmotic (EO) pumping as a mechanism for dynamic control of capillary flow in μPADs. We show that the pump can accelerate or decelerate the baseline capillary-driven velocity, shortening capillary filling by as much as 10-fold, as well as serve as a tunable valve that reversibly switches the flow on and off in an electrically controlled manner.