Rapid enrichment of biomolecules using simultaneous liquid and particulate dielectrophoresis

Abstract

Here we show that dielectrophoretic (DEP) liquid actuation can be used to dispense arrays of nanoliter-sized droplets loaded with biomolecules. Size-based enrichment of these biomolecules occurs rapidly and simultaneously with the droplet dispensing. The physical mechanism responsible for the effect is the positive DEP force directed toward the electrodes that is imposed by the non-uniform electric field during the very rapid DEP actuated flow before droplet formation. Experiments conducted with a suspension of lambda DNA (molecular weight: 31.5 × 10³ kDa) and lectin protein (120 kDa) containing identical molar concentration shows separation of DNA and protein within the nanolitre sized droplets formed along the electrode. The density ratio of protein to DNA varies smoothly from 1 : 1 in the parent droplet to ∼3 : 1, favoring the smaller sized protein in the daughter droplet dispensed furthest from the parent droplet, ∼2.4 mm from the parent droplet. Experiments conducted with binary protein solutions containing identical molar concentrations of bovine serum albumin (66 kDa) and fibrinogen (340 kDa) reveal that enrichment is enhanced as the length of the electrodes is increased. The density ratio of BSA to fibrinogen varied from 1 : 1 in the parent droplet to ∼1.97 : 1 at the last (tenth) droplet, located approximately 4.2 mm from the parent droplet. The entire process, consisting of droplet dispensing and particle separation, occurs in less than one second.