A microfluidic chip for electrochemical conversions in drug metabolism studies

Abstract

We have designed a microfluidic microreactor chip for electrochemical conversion of analytes, containing a palladium reference electrode and platinum working and counter electrodes. The counter electrode is placed in a separate side-channel on chip to prevent unwanted side-products appearing in the measured spectrograms. Using this chip, cyclic voltammograms are measured in volumes of 9.6 nL. Furthermore the conversion efficiency of ferricyanide is characterized using UV/vis-spectroscopy. We have obtained an on-line conversion of 97% using a flow rate of 1 microL/min. We have used the microreactor chip to study the electrochemical metabolism pathway of amodiaquine using electrochemistry (EC)-liquid chromatography (LC)-mass spectrometry (MS). We have compared our results with measurements obtained with commercially available electrochemical flow-through cells. Using our chip it was possible to obtain similar results. Therefore, we have fabricated an electrochemical cell on-chip which is used successfully in EC-UV/vis and EC-LC-MS experiments.

Electrochemistry-on-chip for on-line conversions in drug metabolism studies

“…We have already shown that a microfluidic electrochemical cell can be used successfully (Odijk et al, 2009) to study, e.g., the metabolic pathway of amodiaquine, a known antimalarial agent. The major benefits of using a microscale electrochemical cell is that diffusion lengths are greatly reduced.…”

“…The previous chip (Odijk et al, 2009) contained a palladium pseudo-reference electrode. Using this metal, the fabrication process is limited to temperatures up to 500 • C. At temperatures above 500 • C the palladium thin-film starts to agglomerate.…”

New technologies for nanobiosensing and their applications to real-time monitoring

“…We obtained a sensitivity of 0.42 nA/µM cm −2 and a detection limit of 216 µM for glutamate, a sensitivity of 0.46 nA/µM cm −2 and a detection limit of 115 µM for glucose, a sensitivity of 1.09 nA/µM cm −2 and a detection limit of 115 µM for lactate. Few works [15], [16] deal with multiple detection of metabolites in cell cultures and none of them has shown the integration of multiple and nanostructured WEs sharing common counter and reference electrode. Instead, the results presented in this work represent a novelty with respect to the state-of-the-art in cell culture monitoring and pave the way to new integrated systems for cell analysis.…”

New Approaches for Carbon Nanotubes-Based Biosensors and Their Application to Cell Culture Monitoring

“…On the other hand, minimizing interferences with cells is much more desirable. Few works [17], [18] deal with multiple detection of metabolites in cell cultures and none of them has shown the integration of multiple and nanostructured working electrodes sharing common counter and reference electrodes. CITSens Bio sensors (C-CIT, Switzerland) are the only device in the market able to perform real-time cell monitoring, even if they do not allow multiple detection on the same platform.…”