Magnetic-based microfluidic platform for biomolecular separation

Abstract

A novel microfluidic platform for manipulation of micro/nano magnetic particles was designed, fabricated and tested for applications dealing with biomolecular separation. Recently, magnetic immunomagnetic cell separation has attracted a noticeable attention due to the high selectivity of such separation methods. Strong magnetic field gradients can be developed along the entire wire, and the miniaturized size of these current-carrying conductors strongly enhances the magnetic field gradient and therefore produces large, tunable and localized magnetic forces that can be applied on magnetic particles and confine them in very small spots. Further increases in the values of the generated magnetic field gradients can be achieved by employing miniaturized ferromagnetic structures (pillars) which can be magnetized by an external magnetic field or by micro-coils on the same chip. In this study, we demonstrate magnetic beads trapping, concentration, transportation and sensing in a liquid sample under continuous flow by employing high magnetic field gradients generated by novel multi-functional magnetic micro-devices. Each individual magnetic micro-device consists of the following components: 1. Cu micro-coils array embedded in the silicon substrate with high aspect ratio conductors for efficient magnetic field generation 2. Magnetic pillar(s) made of the magnetic alloy NiCoP for magnetic field focusing and magnetic field gradient enhancement. Each pillar is magnetized by its corresponding coil 3. Integrated sensing coil for magnetic beads detection 4. Microfluidic chamber containing all the previous components. Magnetic fields of about 0.1 T and field gradients of around 300 T/cm have been achieved, which allowed to develop a magnetic force of 3 x 10(-9) N on a magnetic particle with radius of 1 mum. This force is large enough to trap/move this particle as the required force to affect such particles in a liquid sample is on the order of approximately pN. Trapping rates of up to 80% were achieved. Furthermore, different micro-coil designs were realized which allowed various movement modes and with different step-sizes. These results demonstrate that such devices incorporated within a microfluidic system can provide significantly improved spatial resolution and force magnitude for quick, efficient and highly selective magnetic trapping, separation and transportation, and as such they are an excellent solution for miniaturized mu-total analysis systems.

Microbeads for Sampling and Mixing in a Complex Sample

“…For example, microscale core/coil design [3], current-carrying wires [4], wire matrix [5], and micropatterned conductors [6] have been used for trapping, transport, and catch-and-release of magnetic beads. However, micro-electromagnetic systems are limited to manipulation of small numbers of beads and with low magnetic forces due to Joule heating and complexity concerns.…”

Applications of microelectromagnetic traps

“…Photolithographic techniques enable fabrication of almost any desired MET geometry; as a result the geometry of an MET can be tuned for a specific application. Ramadan et al [18,[21][22][23][24][25][26][27] and Lee et al [20,28] have demonstrated customized MP traps which emphasize the effects of different MET geometries. Simulations of magnetic fields produced by different MET geometries have magnetic field profiles attributed to the shape of the MET and magnetic coupling between conductors or loops.…”

Enhancement of separation efficiency on continuous magnetophoresis by utilizing L/T-shaped microchannels

“…These devices can be categorized into discrete and continuous separator. Discrete separator usually needs three steps (i.e., trap, washing and elution) to complete separation (Choi et al 2002;Drogoff et al 2008;Guo et al 2006;Jiang et al 2006;Lund-Olesen et al 2007;Ramadan et al 2006;Ramadan et al 2009;Smistrup et al 2005). For example, Choi et al (2002) proposed the first on-chip magnetic bead-based immunoassay for protein analysis by utilizing integrated electromagnets.…”

“…The magnetic force generated by electromagnetic microcoils is usually small. To strengthen the magnetic force, electromagnetic microcoils are integrated with magnetic materials at the center by complicated fabrications (Drogoff et al 2008;Ramadan et al 2006;Smistrup et al 2005). However, for these magnetophoretic separators high efficient separation needs large electric current and thus leads to obvious joule heating which would cause unwanted effect in microfluidic devices.…”