Development of centrifugal microfluidic platforms based on polymer microfabrication technology

Resumen

Miniaturization of (bio)analytical systems brings together all the advantages of downscaling by using microfluidic platforms; where laboratory workflows meet and interconnect in order to carry out and improve (bio)chemical analyses. Nowadays, microfluidics technology possesses an enormous toolbox of different fluidic functions that can be joined together on demand to create a solution for a specific analytical procedure. Centrifugal microfluidic platforms have resulted in a new technological approach, known as Lab-on-a-CD, which has gained interest due to its recognized advantages. This free-pulse miniaturized technology solved an important problem related to complex instrumentation for liquid pumping as it only requires a rotatory motor for the displacement of samples and reagents inside platforms. Moreover, centrifugal microfluidic platforms offer two major advantages: the possibility of procuring disposable, easily exchangeable plastic cartridges, and the simultaneous and high-precision handling of multiple small aliquots of reagents and samples. As a result, multiple microfluidic operational units can be integrated in parallel on a single platform or disc. This thesis is focused on the goal of full implementation of lab-on-a-CD technology in the Group of Sensors and Biosensors (GSB) of the Universitat Autònoma de Barcelona (UAB) so as to transmit the acquired knowledge for future design, fabrication and evaluation of centrifugal platforms and perform fully automated laboratory assays on demand. This transfer of knowledge is ongoing but the results obtained demonstrate the high level of implementation of the technology and have allowed the development and integration of different centrifugal microfluidic platforms. The development of complex platforms started with the break-down of laboratory workflows into simple process chains. A further brokedown step was required which focused on design, fabrication and evaluation of so-called fluidic unit operations, and those presented in this work vary from simple structures to more complex fluidic systems. Some of the basic elements are similar to ones that can be found in literature, with variations adapted to our purposes. However, we also implemented both novel approximations of previously-described processes and completely new structures that can classified as new fluidic operations, examples of which are published in recognized journals. This work could not have been completed without suitable manufacturing technology which allowed a fast prototyping of microfluidic platforms. Polymer technology, which is currently used in the Lab-on-a-CD field, was ideal for this purpose. Also important is the implementation of the cyclic olefin co-polymer as the substrate for the development of multilayer microfluidic platforms due to its unique and attractive properties. This thesis is intended as a tool for the design, fabrication and evaluation of microfluidic platforms which use COC as a substrate material. This thesis also describes, for the first time, the link of polymer technology with Low Temperature Co-fired Ceramic (LTCC) technology for the fabrication of COC microfluidic platforms. LTCC technology allowed us to obtain ceramic masters for the hot embossing of microfluidic channels onto COC substrate layers combined with polymer technology microstructuring methods to complete the platforms. Then, micromilling of larger microfluidic motifs enabled the completion of the final microfluidic system. The work concludes with the implementation of different centrifugal microfluidic platforms developed for (bio)analytical purposes with a special focus on the study of the lyophilization process of a polymerase chain reaction (PCR) inside a microfluidic platform, the use of the PCR for the detection of a water pathogen, the determination of different analytes (carbon dioxide, nitrite ion and sulfur dioxide) by using gas diffusion as a separation and concentration method and the automatic nitrite ion determination inside a multiple aliquoting structure platform with pre-stored solid reagents.