Electrokinetic characterization of synthetic protein nanoparticles.

The application of nanoparticle in medicine is promising for the treatment of a wide variety of diseases. However, the slow progress in the field has resulted in relatively few therapies being translated into the clinic. Anisotropic synthetic protein nanoparticles (ASPNPs) show potential as a next-generation drug-delivery technology, due to their biocompatibility, biodegradability, and functionality. Even though ASPNPs have the potential to be used in a variety of applications, such as in the treatment of glioblastoma, there is currently no high-throughput technology for the processing of these particles. Insulator-based electrokinetics employ microfluidics devices that rely on electrokinetic principles to manipulate micro- and nanoparticles. These miniaturized devices can selectively trap and enrich nanoparticles based on their material characteristics, and subsequently release them, which allows for particle sorting and processing. In this study, we use insulator-based electrokinetic (EK) microdevices to characterize ASPNPs. We found that anisotropy strongly influences electrokinetic particle behavior by comparing compositionally identical anisotropic and non-anisotropic SPNPs. Additionally, we were able to estimate the empirical electrokinetic equilibrium parameter (eE EEC) for all SPNPs. This particle-dependent parameter can allow for the design of various separation and purification processes. These results show how promising the insulator-based EK microdevices are for the analysis and purification of clinically relevant SPNPs.

Simultaneous Determination of Linear and Nonlinear Electrophoretic Mobilities of Cells and Microparticles.

Direct-current insulator-based electrokinetics (DC-iEK) is a branch of microfluidics that has demonstrated to be an attractive and efficient technique for manipulating micro- and nano- particles, including microorganisms. A unique feature of DC-iEK devices is that nonlinear EK effects are enhanced by the presence of regions of higher field intensity between the insulating structures. Accurate computational models, describing particle and cell behavior, are crucial to optimize the design and improve the performance of DC-iEK devices. The electrokinetic equilibrium condition (EEEC) is a recently introduced fundamental concept that has radically shifted the perspective behind the analysis of particle manipulation in these microfluidic devices. The EEEC takes into consideration previously neglected nonlinear effects on particle migration and indicates that these effects are central to control particle motion in DC-iEK devices. In this study, we present a simultaneous experimental characterization of linear and nonlinear electrokinetic (EK) parameters, that is, the electrophoretic mobility (µEP(1)), the particle zeta potential (ζP), the EEEC, and the electrophoretic mobility of the second kind (µEP(3)), for four types of polystyrene microparticles and four cell strains. For this, we studied the electromigration of polystyrene microparticles ranging in size from 2 to 6.8 µm, three bacteria strains (B. cereus, E. coli, and S. enterica) and a yeast cell (S. cerevisiae), ranging in size from 1 to 6.3 µm, in a polydimethylsiloxane (PDMS) microfluidic channel with a rectangular cross-section. The results illustrated that electrokinetic particle trapping can occur by linear and nonlinear electrophoresis and electroosmosis reaching an equilibrium, without the presence of insulating posts. The experimentally measured parameters reported herein will allow optimizing the design of future DC-iEK devices for a wide range of applications (e.g., to separate multiple kinds of particles and microorganisms) and for developing computational models that better represent reality.

Creation of an electrokinetic characterization library for the detection and identification of biological cells.

The rising concern over drug-resistant microorganisms has increased the need for rapid and portable detection systems. However, the traditional methods for the analysis of microorganisms can be both resource and time intensive. This contribution presents an alternative approach for the characterization of microorganisms using a microscale electrokinetic technique. The present study aims to develop and validate a library with a novel parameter referred to as the electrokinetic equilibrium condition for each strain, which will allow for fast identification of the studied bacterial and yeast cells in electrokinetic (EK) microfluidic devices. To create the library, experiments with six organisms of interest were conducted using insulator-based EK devices with circle-shaped posts. The organisms included one yeast strain, Saccharomyces cerevisiae; one salmonella strain, Salmonella enterica; two species from the same genus, Bacillus cereus and Bacillus subtilis; and two Escherichia coli strains. The results from these experiments were then analyzed with a mathematical model in COMSOL Multiphysics®, which yielded the electrokinetic equilibrium condition for each distinct strain. Lastly, to validate the applicability EK library, the COMSOL model was used to estimate the trapping conditions needed in a device with oval-shaped posts for each organism, and these values were then compared with experimentally obtained values. The results suggest the library can be used to estimate trapping voltages with a maximum relative error of 12%. While the proposed electrokinetic technique is still a novel approach and the analysis of additional microorganisms would be needed to expand the library, this contribution further supports the potential of microscale electrokinetics as a technique for the rapid and robust characterization of microbes. Graphical abstract.

Erratum: "Low frequency cyclical potentials for fine tuning insulator-based dielectrophoretic separations" [Biomicrofluidics 13, 044114 (2019)].

[This corrects the article DOI: 10.1063/1.5115153.].

Low frequency cyclical potentials for fine tuning insulator-based dielectrophoretic separations.

In this study, we demonstrate the use of cyclical low frequency signals with insulator-based dielectrophoresis (iDEP) devices for the separation of particles of similar characteristics and an experimental method for estimating particle DEP mobilities. A custom signal designer program was created using Matlab® and COMSOL Multiphysics® for the identification of specific low frequency signals aimed at separating particle mixtures by exploiting slight differences in surface charge (particle zeta potential) or particle size. For the separation by surface charge, a mixture of two types of 10 µm particles was analyzed and effectively separated employing both a custom step signal and a sawtooth left signal. Notably, these particles had the same shape, size, and surface functionalization as well as were made from the same substrate material. For the separation by size, a sample containing 2 µm and 5 µm particles was successfully separated using a custom step signal; these particles had the same shape, surface functionalization, were made from the same substrate materials, and had only a small difference in zeta potential (10 mV). Additionally, an experimental technique was developed to estimate the dielectrophoretic mobility of each particle type; this information was then utilized by the signal designer program. The technique developed in this study is readily applicable for designing signals capable of separating micron-sized particles of similar characteristics, such as microorganisms, where slight differences in cell size and the shape of surface charge could be effectively exploited. These findings open the possibility for applications in microbial screening using iDEP devices.