Label-free cellular manipulation and sorting via biocompatible ferrofluids

Abstract

We present a simple microfluidic platform that uses biocompatible ferrofluids for the controlled manipulation and rapid separation of both microparticles and live cells. This low-cost platform exploits differences in particle size, shape, and elasticity to achieve rapid and efficient separation. Using microspheres, we demonstrate size-based separation with 99% separation efficiency and sub-10-m resolution in <45 s. We also show continuous manipulation and shape-based separation of live red blood cells from sickle cells and bacteria. These initial demonstrations reveal the potential of ferromicrofluidics in significantly reducing incubation times and increasing diagnostic sensitivity in cellular assays through rapid separation and delivery of target cells to sensor arrays.ferromicrofluidics ͉ magnetic hole ͉ cell separation

Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

“…The associated device is inexpensive and simple, only requiring a channel and hand-held permanent magnets. Sorting specificity of this approach is not limited to size difference only; it is also sensitive to cells' shape and deformability (Kose et al 2009). In adapting it to miniaturized flow cytometry, ferrohydrodynamic manipulation can first focus cells into single cell streams before sorting, eliminating needs for excessive sheath flow and preventing sample dilution (Zhu et al 2011a).…”

“…Although these are stringent requirements, progress has been made towards synthesizing biocompatible ferrofluids. For example, Koser's group used citrate to stabilize cobalt-ferrite nanoparticles for live red blood cell and Escherichia coli cell sorting (Kose et al 2009). Yellen's group used Bovine Serum Albumin (BSA) to stablize magnetite nanoparticles for human umbilical vein endothelial cells manipulation (Krebs Melissa et al 2009).…”

“…To address problems with label-based magnetophoresis, a label-free technique that uses reverse magnetophoresis to manipulate and sort cells has been developed recently based on ferrofluid hydrodynamics (ferrohydrodynamics) (Yellen et al 2005;Kose et al 2009;Zhu et al 2010;Zhu et al 2011a;Kose and Koser 2012). Ferrofluids are colloidal suspensions of magnetic nanoparticles, typically magnetite (Fe 3 O 4 ) with approximately 10 nm diameters (Rosensweig 1985).…”

“…However, magnetic susceptibility of paramagnetic salt solutions is inherently small, about 5 orders of magnitude weaker than that of a ferrofluid (Krebs Melissa et al 2009), rendering slower manipulation speed and low throughput. As a result of the higher susceptibility of ferrofluids, Koser's group was able to use an integrated microfluidic platform for sorting of microparticles and live cells within a citrate stabilized cobalt-ferrite ferrofluid in static flow conditions (Kose et al 2009). The same device was also applied to continuous-flow frequency-adjustable particles separation (Kose and Koser 2012).…”

Magnetophoretic circuits for digital control of single particles and cells

“…The desired capabilities of single-cell arrays bear strong resemblance to random access memory (RAM) computer chips, including the ability to introduce and retrieve single cells from precise locations of the chip (writing data), and query the biological state of specified cells at future time points (reading data). Existing particle handling tools based on hydrodynamic [8][9][10][11] , optic [12][13][14][15][16][17][18] , electric [19][20][21][22] and magnetic [23][24][25][26][27][28][29][30][31][32][33][34][35][36] trapping forces can achieve parts of this desired functionality; however, no single technique to our knowledge encompasses the scalability, flexibility and automation that allows single-cell chips to perform with the level of integration of computer circuits.…”