Microfluidic Gradient Titration: A Lab-on-Chip Platform for Continuous Chemical Analysis

Titration is the oldest quantitative method of analytical chemistry: a reagent of known concentration is added to a sample until an endpoint signals that all analyte has reacted. The principle has not changed in two centuries; endpoints are still found by adding titrant stepwise and watching a signal change in time. Titrators therefore remain bench-top instruments that need milliliter samples, moving parts and an operator. The most important variant, Karl Fischer water determination, is performed about half a million times per day in pharmaceutical and petrochemical quality control on exactly such instruments. This project moves titration from time to space. In a microchannel that connects a titrant solution to the sample, titrant and analyte diffuse toward each other and react. A stationary concentration profile forms, and the position at which the two are consumed in equal amounts, the equivalence point, encodes the analyte concentration. Instead of dosing reagent and waiting for an endpoint, the signal is read continuously: when the sample composition changes, the equivalence point moves. Microchannel designs recently developed by imec suppress parasitic flow in such gradient channels and remove the main obstacle to a stable titration in space. The PhD combines three lines of work: fabrication of microfluidic chips, control of gradients and flows with integrated readout, and simulation of the coupled reaction–diffusion problem. Readout starts with fluorescence imaging and progresses to on-chip electrochemical detection, with bi-amperometric electrodes for Karl Fischer chemistry and imec's extended-gate field-effect transistors (EGFETs) as pH sensors for acid-base titration. The project will result in two demonstrators: quantification of short-chain fatty acids, principal metabolic markers of the gut microbiome, relevant to ingestible sensing at OnePlanet; and determination of trace water by Karl Fischer chemistry, relevant to a large installed industrial market.