Label-Free Detection of Biomolecules in Microfluidic Systems Using On-Chip UV and Impedimetric Sensors

Label-free approaches to biomolecular detection in microfluidics avoid potential labeling interference, are suitable for the screening of analytes that are not easily tagged, and simplify assay development toward point-of-use applications. In this paper, multimodal label-free detection of biomolecules was performed in a microfluidic system: 1) optically, with an integrated hydrogenated amorphous silicon thin-film photodiode and 2) electrically, using integrated electrochemical impedance interdigitated microelectrodes. Bovine serum albumin, single-stranded DNA, and a mixture of human immunoglobulins G were selected as model biomolecules. The sensitivities of the biomolecular detection were first evaluated in a bare microfluidic channel. The lower limit of detection obtained, for each transducing technique, was 10 nM for the impedimetric detection of ssDNA and 80 nM for the optical detection of a mixture of antibodies. These sensitivities were considered fit-for-purpose when applied to microfluidic systems aimed at monitoring molecular adsorption to different immobilized ligands. To validate the proposed multimodal detection, the model biomolecules were detected in a microfluidic structure packed with ion exchange chromatography agarose microbeads and the target biomolecules were monitored in real time both at bead level and downstream of the packed beads. The application of these label-free sensors ranges from bioprocess optimization to molecular purification and potentially the development of rapid analytics, with the advantages of device compactness, cost effectiveness, high speed of analysis, and multiplexed signal acquisition.