Dielectrophoresis: An Approach to Increase Sensitivity, Reduce Response Time and to Suppress Nonspecific Binding in Biosensors?

Abstract

The performance of receptor-based biosensors is often limited by either diffusion of the analyte causing unreasonable long assay times or a lack of specificity limiting the sensitivity due to the noise of nonspecific binding. Alternating current (AC) electrokinetics and its effect on biosensing is an increasing field of research dedicated to address this issue and can improve mass transfer of the analyte by electrothermal effects, electroosmosis, or dielectrophoresis (DEP). Accordingly, several works have shown improved sensitivity and lowered assay times by order of magnitude thanks to the improved mass transfer with these techniques. To realize high sensitivity in real samples with realistic sample matrix avoiding nonspecific binding is critical and the improved mass transfer should ideally be specific to the target analyte. In this paper we cover recent approaches to combine biosensors with DEP, which is the AC kinetic approach with the highest selectivity. We conclude that while associated with many challenges, for several applications the approach could be beneficial, especially if more work is dedicated to minimizing nonspecific bindings, for which DEP offers interesting perspectives.

Trapping proteins on nanopores by dielectrophoresis

“…When applied to proteins, their relatively small size, R 0 ∼ 1 nm, yields a force too low to trap a protein at the practical field strength E ≤ 100 kV/cm. [9][10][11][12] Nevertheless, Washizu et al demonstrated protein trapping with fields E ∼ 10 kV/cm, an order of magnitude smaller than expected. 13 This observation had remained puzzling 14 until it was recognized that a large intrinsic permanent dipole moment of a protein produces an induced dipole M 0 E nearly four orders of magnitude higher than what follows for the induced dipole from the CM factor.…”

“…This theoretical prediction opened the door to applications of DEP to protein trapping and a number of potential systems where such effects can be realized have been identified. 6,12,[16][17][18][19][20][21] It is now increasingly appreciated that DEP susceptibilities of proteins are mostly consistent between different reports 6,19,22 and do not follow dielectric predictions based on the CM factor. [22][23][24][25] The electric field magnitude required for trapping the protein can be estimated by a balancing condition equating the magnitude of the free energy |F E | to the thermal kinetic energy of the particle: 6,13,26 (3/2)k B T .…”