Ashok Sinha

Magnetic microsphere-based mixers for microdroplets

While droplet-based microfluidic systems have several advantages over traditional flow-through devices, achieving adequate mixing between reagents inside droplet-based reactors remains challenging. We describe an active mixing approach based on the magnetic stirring of self-assembled chains of magnetic microspheres within the droplet as these stirrers experience a rotating magnetic field. We measure the mixing of a water-soluble dye in the droplet in terms of a dimensional mixing parameter as the field-rpm, fluid viscosity, and microsphere loading are parametrically varied. These show that the mixing rate has a maximum value at a critical Mason number that depends upon the operating conditions.

Single Magnetic Particle Dynamics in a Microchannel

Functionalized magnetic particles are used in micrototal analysis systems since they act as magnetically steered mobile substrates in microfluidic channels, and can be collected for bioanalytical processing. Here, we examine the motion of magnetic microbeads in a microfluidic flow under the influence of a nonuniform external magnetic field and characterize their collection in terms of the magnetic field strength, particle size, magnetic susceptibility, host fluid velocity and viscosity, and the characteristic length scale. We show that the collection efficiency of a magnetic collector depends upon two dimensionless numbers that compare the magnetic and particle drag forces.

Numerical investigation of flow-through immunoassay in a microchannel

Immunomagnetic separation (IMS) is a method to isolate biomaterials from a host fluid in which specifically selected antibodies attached to magnetic particles bind with their corresponding antigens on the surface of the target biological entities. A magnet separates these entities from the fluid through magnetophoresis. The method has promising applications in microscale biosensors. We develop a comprehensive model to characterize the interaction between target species and magnetic particles in microfluidic channels. The mechanics of the separation of target nonmagnetic N particles by magnetic M particles are investigated using a particle dynamics simulation. We consider both interparticle magnetic interactions and the binding of the functionalizing strands of complementary particles. The temporal growth of a particle aggregate and the relative concentrations of M and N particles are investigated under different operating conditions. A particle aggregate first grows and then exhibits periodic washaway abo...

Magnetically Assembled 3-D Mesoscopic Patterns Using Suspension of Superparamagnetic Nanoparticles

A self assembly process is characterized by the spontaneous and ordered aggregation of similar components. At the nanoscale, these constituents can be colloids, or other nanoparticles that combine to form structures of meso- and macroscopic dimensions. Self assembly is most evident during the growth of biological structures. Due to its natural elegance, there is considerable interest in investigating similar methods in other fields of sciences. In principle, the process of dynamic self assembly is characterized by a competition between at least two forces — one attractive and the other repulsive — in thermodynimacally nonequilibrium systems. Several researchers have described self assembly in configurations where biological [1] or chemical [2] mediation, electrostatic [3], capillary [4] or fluid dynamic [5] forces have provided a motive potential.Copyright

Immunomagnetic Separation in Microchannels: From MEMS to BioNEMS

Conventional methods of monitoring and testing water quality involve collection of the sample to be tested and its subsequent analysis in a research laboratory for which some procedures may not be feasible or even accessible under certain field situations. Therefore, next generation sensors are required. Herein, an innovative concept that combines a micromixer and microparticle trap is proposed that should enable more rapid pathogen detection in contaminated water. In it, immunomagnetic separation (a procedure [1,2] that is well practiced in the field of immunochemistry) is scaled down from the benchtop to the microscale. Our design is generic, i.e., design is not limited to the detection of waterborne biological agents, but can be used for other forms of chemical analysis. Testing for waterborne bacteria requires analysis methods that must meet a number of challenging criteria. Time and sensitivity of analysis are the more important limitations. Bacterial detection methods have to be rapid and very sensitive since the presence of even a small pathogenic sample may sometimes constitute an infectious or otherwise harmful dose. Selective detection is also required because small numbers of pathogenic bacteria are often present in a complex biological environment along with many other nonpathogenic organisms. As an example, the infectious dosage of a pathogen such as E. coli O157:H7 or Salmonella is as low as 10 cells and the existing coliform standard for E. coli in water is 4 cells: 100 ml [3].Copyright

Magnetic Micromanipulation of a Single Magnetic Microsphere in a Microchannel

Magnetic microspheres are well known for their ability to provide high surface-to-volume ratio mobile reaction surfaces for chemical and biochemical reactions. Their use in microfluidic devices opens up novel avenues for uses in ‘lab-on-a-chip’ applications, e.g., as magnetic tweezers. Cantilevers and optical tweezers are widely used for micromanipulating cells or biomolecules in order to measure their mechanical properties, or for biosensor applications. However, they do not allow for ease of rotary motion and can sometimes damage the handled material. We present herein a system of magnetic tweezers that uses functionalized magnetic microspheres as mobile substrates for biological and biochemical reactions and offers better manipulation of the cells or organic molecules. The predominant transport issue for these magnetic tweezers is the precise magnetic manipulations of the microbeads so that the chemical/biological reactions at the bead surface are controlled. The best way to obtain unambiguous information about the behavior of particles is to begin with the study of a single isolated particle in a microchannel flow. We have conducted a fundamental study to manipulate an isolated magnetic microparticle using the concept of ‘action-at-a-distance’. An external magnetic field is used to direct and steer the particle across a microchannel. Such a study is directly pertinent to practical applications where usually a small number of such microspheres are utilized, such as DNA sequencing and separation, cell manipulation and separation, exploration of complex biomolecules by specific binding enabling folding and stretching, etc. Numerical simulation of the microchannel flow and particle manipulation is performed using a finite-volume transient CFD code and Lagrangian tracking of magnetic microspheres in the flow under an imposed magnetic field gradient. Experimental validation of the numerical results is then performed. The effects of varying viscosity and flowrate using two different particle sizes are investigated. Parametric study is performed to tune the external magnetic field so as to obtain a desired particle trajectory. Finally, the proof of concept demonstration of the magnetic tweezing is reported. We conclude that magnetic tweezers are viable and can be fabricated as part of a biocompatible setup that could become a suitable alternative to the other available micromanipulators.Copyright

Magnetic Targeting of Particle Transport Under Pulsatile Flow

Magnetic Drug Targeting (MDT) has been shown to be a promising technique to effectively deliver medicinal drugs via functionalized [1] magnetic particles to target sites during the treatment of cancer and other diseases [2,3,4]. In this paper, we investigate the interaction of steady and pulsatile flows injected with a ferrofluid, which is a colloidal suspension of superparamagnetic nanoparticles in a glass tube under the influence of a magnetic field. Ferrofluids are colloidal suspensions of single domain magnetic nanoparticles that are of the order of 10 nm in diameter. In this experiment, the ferrofluid particles were directed to a particular region of interest within a 10 mm diameter glass vessel by means of an applied localized magnetic field that originated outside of the vessel. The magnetic field was generated using a rare earth sintered permanent magnet which produced the magnetic field gradient required for inducing a body force on the volume of the ferrofluid. The experimental results reveal flows with rich dynamical phenomena. The aggregation of the ferrofluid produces a self-assembled hemispherical structure which dynamically interacts with the host flow. The aggregation generates an occlusion creating a flow field that is similar to that past an obstruction. However, since the structure itself is of a fluidic nature, it is subject to shear forces caused by the host fluid. In addition, the wake of the flow behind the aggregation creates vortices which are critical to study the stability of the ferrofluid aggregate. This paper presents a detailed investigation of the dynamics of the flow using Time-Resolved Digital Particle Image Velocimetry. To the best of the authors’ knowledge, these are the first quantitative, spatiotemporally resolved measurements documenting the interaction of a host fluid with a ferrofluid aggregate under steady or pulsatile flow conditions.Copyright