Roozbeh Abedini-Nassab

Magnetophoretic circuits for digital control of single particles and cells

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.

Characterizing the Switching Thresholds of Magnetophoretic Transistors

The switching thresholds of magnetophoretic transistors for sorting cells in microfluidic environments are characterized. The transistor operating conditions require short 20-30 mA pulses of electrical current. By demonstrating both attractive and repulsive transistor modes, a single transistor architecture is used to implement the full write cycle for importing and exporting single cells in specified array sites.

Optimization of magnetic switches for single particle and cell transport

The ability to manipulate an ensemble of single particles and cells is a key aim of lab-on-a-chip research; however, the control mechanisms must be optimized for minimal power consumption to enable future large-scale implementation. Recently, we demonstrated a matter transport platform, which uses overlaid patterns of magnetic films and metallic current lines to control magnetic particles and magnetic-nanoparticle-labeled cells; however, we have made no prior attempts to optimize the device geometry and power consumption. Here, we provide an optimization analysis of particle-switching devices based on stochastic variation in the particles size and magnetic content. These results are immediately applicable to the design of robust, multiplexed platforms capable of transporting, sorting, and storing single cells in large arrays with low power and high efficiency.

Dynamic trajectory analysis of superparamagnetic beads driven by on-chip micromagnets

We investigate the non-linear dynamics of superparamagnetic beads moving around the periphery of patterned magnetic disks in the presence of an in-plane rotating magnetic field. Three different dynamical regimes are observed in experiments, including (1) phase-locked motion at low driving frequencies, (2) phase-slipping motion above the first critical frequency fc1, and (3) phase-insulated motion above the second critical frequency fc2. Experiments with Janus particles were used to confirm that the beads move by sliding rather than rolling. The rest of the experiments were conducted on spherical, isotropic magnetic beads, in which automated particle position tracking algorithms were used to analyze the bead dynamics. Experimental results in the phase-locked and phase-slipping regimes correlate well with numerical simulations. Additional assumptions are required to predict the onset of the phase-insulated regime, in which the beads are trapped in closed orbits; however, the origin of the phase-insulated state appears to result from local magnetization defects. These results indicate that these three dynamical states are universal properties of bead motion in non-uniform oscillators.

Monolithically integrated Helmholtz coils by 3-dimensional printing

3D printing technology is of great interest for the monolithic fabrication of integrated systems; however, it is a challenge to introduce metallic components into 3D printed molds to enable broader device functionality. Here, we develop a technique for constructing a multi-axial Helmholtz coil by injecting a eutectic liquid metal Gallium Indium alloy (EGaIn) into helically shaped orthogonal cavities constructed in a 3D printed block. The tri-axial solenoids each carry up to 3.6 A of electrical current and produce magnetic field up to 70 G. Within the central section of the coil, the field variation is less than 1% and is in agreement with theory. The flow rates and critical pressures required to fill the 3D cavities with liquid metal also agree with theoretical predictions and provide scaling trends for filling the 3D printed parts. These monolithically integrated solenoids may find future applications in electronic cell culture platforms, atomic traps, and miniaturized chemical analysis systems based on nuclear magnetic resonance.

Nanotechnology and Nanopore Sequencing.

DNA sequencing is one of the crucially important tasks in the fields of genetics and cellular biology, which is benefiting from nanotechnology. DNA carries genetic information and sequencing it in a quick way helps researchers in achieving essential goals, including personalized medicine. Solid state nanopores potentially can offer more durability, in sequencing biomolecules, over the proteinbased nanopores. In recent years, various ideas are introduced towards the goal of fast and low cost sequencing. In this review article recent advances presented in journal articles as well as patents in this field, including sequencing methods, membrane materials and their fabrication techniques, drilling methods, and biomolecule translocation speed control ideas are investigated.

Automated single cell arrays based on magnetophoretic circuits

D (Dz) are small catalytic DNA molecules, which can catalyze a variety of chemical reactions. Due to their structural versatility, biocompatibility, signal amplification ability and relatively low cost, Dz are widely used as scaffolds for biosensor design. Here, we present a split Dz (sDz) approach for nucleic acid sensors. A Dz is divided into two subunits, which are not catalytically active in the absence of a nucleic acid target due to spatial separation. When target is present, the two subunits are brought in proximity and the catalytic core is re-formed. As a result, target-inducable signal is generated and can be monitored for target detection and quantification. The binary design enables great selectivity because each of the two short probe-analyte hybrids is very sensitive to even a slight imperfection in the sequence of the analyzed nucleic acid. Using this approach, we have designed sDz sensors targeting rRNA of Escherichia coli, Mycobacterium tuberculosis and M. absesses, which are important human pathogens. We have demonstrated that the sensors are capable of differentiation between Single Nucleotide Substitutions (SNSs) in the analyzed sequences. Therefore, it is possible to use sDz for SNSs and strain genotyping, as well as for drug susceptibility testing of bacterial pathogens. sDz sensors can be also employed for rRNA maturation monitoring and mutation analysis. The sensors can generate either fluorescent signal or color change. In their later implementation, sDz sensors can be used for point-of-care diagnostics of bacterial pathogens.

Modeling in vivo dynamics of RNA polymerase II meeting Nucleosomes

Nucleosomes are shown to be barriers for RNA Polymerase II elongation along DNA, and their entry site behaves as the major obstacle. In this work, based on recent available in vivo data, we introduce a mathematical model for RNA Polymerase II reads. Moreover, as an alternative way, we use Radial Basis Function Network to predict RNA Polymerase II reads. Results of our models are in good agreement with experimental data. Furthermore, we introduce a random walk model which includes stalling, backtracking, and elongation phenomena. This model can predict and simulate the RNA Polymerase II trajectory on DNA, when it meets various nucleosomes.