Particle-Based Microfluidic Quartz Crystal Microbalance (QCM) Biosensing Utilizing Mass Amplification and Magnetic Bead Convection

Microfluidic quartz crystal microbalances (QCM) can be used as powerful biosensors that not only allow quantifying a target analyte, but also provide kinetic information about the surface processes of binding and release. Nevertheless, their practical use as point-of-care devices is restricted by a limit of detection (LoD) of some ng/cm². It prohibits the measurement of small molecules in low concentrations within the initial sample. Here, two concepts based on superparamagnetic particles are presented that allow enhancing the LoD of a QCM. First, a particle-enhanced C-reactive protein (CRP) measurement on a QCM is shown. The signal response could be increased by a factor of up to five by utilizing the particles for mass amplification. Further, a scheme for sample pre-preparation utilizing convective up-concentration involving magnetic bead manipulation is investigated. These experiments are carried out with a glass device that is fabricated by utilizing a femtosecond laser. Operation regimes for the magnetic manipulation of particles within the microfluidic channel with integrated pole pieces that are activated by external permanent magnets are described. Finally, the potential combination of the concepts of mass amplification and up-concentration within an integrated lab-on-a chip device is discussed.