Dileep Mampallil

Electrochemical single-molecule detection in aqueous solution using self-aligned nanogap transducers.

Electrochemical detection of individual molecular tags in nanochannels may enable cost-effective, massively parallel analysis and diagnostics platforms. Here we demonstrate single-molecule detection of prototypical analytes in aqueous solution based on redox cycling in 40 nm nanogap transducers. These nanofluidic devices are fabricated using standard microfabrication techniques combined with a self-aligned approach that minimizes gap size and dead volume. We demonstrate the detection of three common redox mediators at physiological salt concentrations.

Reversible Adsorption of Outer-Sphere Redox Molecules at Pt Electrodes

Adsorption often dominates the response of nanofluidic systems due to their high surface-to-volume ratios. Here we harness this sensitivity to investigate the reversible adsorption of outer-sphere redox species at electrodes, a phenomenon that is easily overlooked in bulk measurements. We find that even though adsorption does not necessarily play a role in the electron-transfer process, such adsorption is nevertheless ubiquitous for the widely used outer-sphere species. We investigate the physical factors driving adsorption and find that this counterintuitive behavior is mediated by the anionic species in the supporting electrolyte, closely following the well-known Hofmeister series. Our results provide foundations both for theoretical studies of the underlying mechanisms and for contriving strategies to control adsorption in micro/nanoscale electrochemical transducers where surface effects are dominant.

Redox Couples with Unequal Diffusion Coefficients: Effect on Redox Cycling

Redox cycling between two electrodes separated by a narrow gap allows dramatic amplification of the faradaic current. Unlike conventional electrochemistry at a single electrode, however, the mass-transport-limited current is controlled by the diffusion coefficient of both the reduced and oxidized forms of the redox-active species being detected and, counterintuitively, by the redox state of molecules in the bulk solution outside the gap itself. Using a combination of finite-element simulations, analytical theory, and experimental validation, we elucidate the interplay between these interrelated factors. In so doing, we generalize previous results obtained in the context of scanning electrochemical microscopy and obtain simple analytical results that are generally applicable to experimental situations where efficient redox cycling takes place.

Controlling flow patterns in oscillating sessile drops by breaking azimuthal symmetry

We study time-averaged flows within sessile drops that oscillate under the influence of an AC voltage applied in electrowetting configuration. We show that the average flow velocity in the azimuthal plane correlates with the eigenmodes of the drop in the polar direction and—most importantly—we demonstrate that the azimuthal symmetry of the flow fields can be broken by introducing pinning sites along the contact line of the drop. We anticipate that the controlled introduction of azimuthal vortices increases the mixing efficiency inside the droplet.

A simple method to determine the surface charge in microfluidic channels

We study EOF through microchannels, made of glass or glass‐PDMS, by displacing an electrolyte solution at given concentration with the same electrolyte at a different concentration via an external electric field. When a constant voltage is applied over the channel, the electric current through the channel varies during the displacement process. We propose a simple analytical model that describes the time dependence of the current regardless of the concentration ratio chosen. With this model, which is applicable beyond the Debye–Hückel limit, we are able to quantify the EOF velocity and to determine the surface charge on the microchannel walls from the measured current behavior, as well as the zeta potential at given local electrolyte concentration.

Chemical-free lysis and fractionation of cells by use of surface acoustic waves for sensitive protein assays

We exploit the mechanical action of surface acoustic waves (SAW) to differentially lyse human cancer cells in a chemical-free manner. The extent to which cells were disrupted is reported for a range of SAW parameters, and we show that the presence of 10 μm polystyrene beads is required to fully rupture cells and their nuclei. We show that SAW is capable of subcellular fractionation through the chemical-free isolation of nuclei from whole cells. The concentration of protein was assessed in lysates with a sensitive microfluidic antibody capture (MAC) chip. An antibody-based sandwich assay in a microfluidic microarray format was used to detect unlabeled human tumor suppressor protein p53 in crude lysates, without any purification step, with single-molecule resolution. The results are digital, enabling sensitive quantification of proteins with a dynamic range >4 orders of magnitude. For the conditions used, the efficiency of SAW-induced mechanical lysis was determined to be 12.9% ± 0.7% of that for conventional detergent-based lysis in yielding detectable protein. A range of possible loss mechanisms that could lead to the drop in protein yield are discussed. Our results show that the methods described here are amenable to an integrated point-of-care device for the assessment of tumor protein expression in fine needle aspirate biopsies.

Sample preconcentration inside sessile droplets using electrowetting

Electrowetting with alternate voltage (AC) creates azimuthal flow vortices inside sessile droplets. These flow vortices can be controlled by introducing pinning sites at the contact line. When the frequency of the applied AC voltage is gradually ramped from a few hundreds of hertz to a few tens of kilohertz the azimuthal flow vortices contract and move towards the contact line near the pinning site. Dispersed particles in the liquid are collected in the center of these vortices leading to an increase in the local particle concentration by up to more than one order of magnitude. We provide a qualitative explanation for symmetry of the flow patterns within the drops and discuss possible scenarios explaining the particle collection and preconcentration.

Acoustic suppression of the coffee-ring effect

We study the influence of acoustic fields on the evaporative self-assembly of solute particles suspended inside sessile droplets of complex fluids. The self-assembly process often results in an undesirable ring-like heterogeneous residue, a phenomenon known as the coffee-ring effect. Here we show that this ring-like self-assembly can be controlled acoustically to form homogeneous disc-like or concentrated spot-like residues. The principle of our method lies in the formation of dynamic patterns of particles in acoustically excited droplets, which inhibits the evaporation-driven convective transport of particles towards the contact line. We elucidate the mechanisms of this pattern formation and also obtain conditions for the suppression of the coffee-ring effect. Our results provide a more general solution to suppress the coffee-ring effect without any physiochemical modification of the fluids, the particles or the surface, thus potentially useful in a broad range of industrial and analytical applications that require homogenous solute depositions.

Electroosmotic shear flow in microchannels.

We generate and study electroosmotic shear flow in microchannels. By chemically or electrically modifying the surface potential of the channel walls a shear flow component with controllable velocity gradient can be added to the electroosmotic flow caused by double layer effects at the channel walls. Chemical modification is obtained by treating the channel wall with a cationic polymer. In case of electric modification, we used gate electrodes embedded in the channel wall. By applying a voltage to the gate electrode, the zeta potential can be varied and a controllable, uniform shear stress can be applied to the liquid in the channel. The strength of the shear stress depends on both the gate voltage and the applied field which drives the electroosmotic shear flow. Although the stress range is still limited, such a microchannel device can be used in principle as an in situ micro-rheometer for lab on a chip purposes.