Microfluidic devices for biotechnology and organic chemical applications

Abstract: Imagine if you could combine the power and capabilities ofan entire laboratory in the palm of your hand. Advances inmicrofluidic chip technology promise to integrate andminiaturize multiple lab processes into a single palm-sizeddevice. The advantages of these lab-on-a-chip devices,sometimes also referred to as micro total analysis systems(µTAS), compared with conventional bench-scale systems arenumerous and wide ranging and include: less reagentconsumption, low manufacturing costs, increased performance,faster analysis, high sample throughput, integration andautomation possibilities, and disposability. However,microfluidic devices also present challenges such as theinterfacing to the macro world and detection limits.In this thesis the focus has been to develop novel discretemicrofluidic components for biotechnology and organic chemicalapplications with the goal to integrate them to formlab-on-chips. A flow-through filter-chamber device has beendesigned, manufactured and evaluated for chemical analysis onbeads. Passive liquid handling has been integrated on the chipin the form of hydrophobic valves at the inlet channels. Anarray format has also been developed to allow parallel analysisof multiple samples. The filter-chamber functions well forsingle nucleotide analysis using pyrosequencing. Initialevaluations on catalyst screening in the filter-chamber devicehas been performed.The suitability of valve-less micropumps for biochemicalapplications is presented. Fluids encountered in variousbiochemical methods, including living cells, that areproblematic for other micropumps have been pumped with goodperformance. This thesis also introduces expandablemicrospheres as a novel component in microfluidics includingapplications such as one-shot valves, micropositioning andsurface enlargement.A novel technique for bead immobilization in microfluidicdevices based on surface chemistry is presented in this thesis.Beads for both biochemical assays and organic chemistry havebeen self-sorted and self-assembled in line patterns as narrowas 5 µm on both structured and unstructured substrates.This method will greatly facilitate the generation of screeningplatforms, for example.To develop a microfluidic device for catalysis-on-chip,ligands for asymmetric catalysis have successfully beenimmobilized in silicon channels by consecutive microcontactprinting, which is a novel technique presented in thisthesis.Keywords:microfluidics, beads, microspheres, silicon,filter-chamber, flow-through, bead trapping, DRIE, passivevalves, fluorocarbon, microfluidic array, adhesive bonding,valve-less micropump, microcontact printing, PDMS,self-assembly, self-sorting, DNA, SNP, pyrosequencing,allele-specific extension, expandable microspheres, catalysis,chiral ligand, monolayer, miniaturization, lab-on-a-chip,µTAS.