Parallelizable Microfluidic Resistive On-Line Detector of Micrometric Aggregates of Biopharmaceutical Antibodies

Abstract

A microfluidic device based on the differential measurement of the ionic resistance of a micropore for detection of aggregates of antibodies in biopharmaceutical downstream process is presented. The main novelty of this contribution regards the experimental demonstration that, despite the poor solidness of proteins, their aggregates, in their standard production buffer, can be electrically detected down to 2.4 μm diameter with sub-ms transit time (flow rate of 5 μl/min). Thanks to the simple PDMS fluidic fabrication, compact DC readout circuit and convenient use of the same metallic silver tubing for both electrical and fluidic interconnection, the device can be straightforwardly parallelized in tens of units, thus combining single micrometric sensitivity with larger flow rates (>100 μl/min), suitable for in-line installation in pharmaceutical plants

Resistive pulse sensing as particle counting and sizing method in microfluidic systems: Designs and applications review

“…The spectrum of suitable materials is wide ranging from platinum [18,19,23,25,30], silver [24], copper [26], or special Ag/AgCl electrodes [13,31,32]. An interesting approach was the use of silver tubing for both electrical and fluidic connection [33].…”

“…Since the sensitivity has to be levered with the speed of detection, their device was able to detect polystyrene beads (2 μm in diameter) at the flow rate of 10 μL/min with a counting rate up to 1 kbeads/s. Similarly, the antibody aggregates ranging from 2.4 to 7 μm (protein aggregates do not have the same insulating properties as polystyrene beads) at the flow rate of 5 μL/min and the average pulse width of 200 μs could be detected .…”

Advances in High-Resolution Microscale Impedance Sensors

“…Thanks to the ohmic contact of nonpolarizable electrodes, the ionic resistance is measured in DC, allowing great simplicity in the readout circuit. This technique proved to be very powerful and has been extended from cells, reducing the size of the pore down to nanometric dimensions, also to detect nanoparticles at high speed [20], DNA molecules (for label-free sequencing) [21], and bacteria [22] and clusters of antibodies in pharmaceutical plants [23].…”