Now showing 1 - 3 of 3
  • Publication
    Novel nonlinear magnetophoretic systems for on-chip separation and biosensing
    (University College Dublin. School of Chemistry  , 2015) ; ;
    Nonlinear magnetophoresis (NLM) is a recently introduced technique for onchiptransport and separation of superparamagnetic (SPM) beads based on atravelling magnetic eld wave generated by the combination of a micromagnetarray (MMA) and an applied rotating magnetic eld. The potential of this methodhas been demonstrated for the controlled transport and isolation of bead-labelled biological targets, such as, cells and exosomes. The high-resolution separation of dierent bead populations based on size, magnetic susceptibility, and presence of a captured analyte has also been reported.This PhD project aimed to develop and characterize dierent micromagnet designsfor the NLM transport of SPM beads and labelled biological targets, and to identifynovel separation and biosensing strategies. The SPM beads were used to capture different molecules, i.e. biotinylated bovine serum albumine and double stranded DNAfrom herpes-simplex-virus 1, and the induced bead aggregation provided a mean toisolate and detect the labelled analytes. With the NLM chip it was possible to separatethe unreacted beads from the beads carrying the target. These results showedthe potential of the technique to be used in magnetic bead aggregation (MBA) assaysand provided fabrication guidelines for the design of more complex arrays. Two innovative micromagnet designs were proposed that allowed SPM beads to be focusedand separated on-chip. These new architectures were used to rapidly collect the SPMbeads from a large region of the chip and focus them into synchronized lines, withthe aim of integrating a dedicated detection system. Tri{magnet switching junctionswere used to control the transport of the beads and to separate them based on theirsize in a continuous manner. The controlled transport of SPM bead-labelled singleMDA-MB-231 cells has also been demonstrated. The micromagnet designs presentedhere promise to allow more complex micromagnet networks to be developed, aimingtowards the creation of fully-functional miniaturized biosensors.
  • Publication
    A microfluidic dual gradient generator for conducting cell-based drug combination assays
    We present a microfluidic chip that generates linear concentration gradients of multiple solutes that are orthogonally-aligned to each other. The kinetics of gradient formation was characterized using a fluorescent tracer matching the molecular weight of small inhibitory drugs. Live-cell signalling and motility experiments were conducted to demonstrate the potential uses and advantages of the device. A431 epidermoid carcinoma cells, where EGF induces apoptosis in a concentration-dependent manner, were simultaneously exposed to gradients of MEK inhibitor and EGF receptor (EGFR) inhibitor. By monitoring live caspase activation in the entire chip, we were able to quickly assess the combinatorial interaction between MEK and EGFR pathways, which otherwise would require costly and time consuming titration experiments. We also characterized the motility and morphology of MDA-MB-231 breast cancer cells exposed to orthogonal gradients of EGF and EGFR inhibitor. The microfluidic chip not only permitted the quantitative analysis of a population of cells exposed to drug combinations, but also enabled the morphological characterization of individual cells. In summary, our microfluidic device, capable of establishing concentration gradients of multiple compounds over a group of cells, facilitates and accelerates in vitro cell biology experiments, such as those required for cell-based drug combination assays.
      449Scopus© Citations 20
  • Publication
    Micromagnet arrays for on-chip focusing, switching, and separation of superparamagnetic beads and single cells
    Nonlinear magnetophoresis (NLM) is a powerful approach for on-chip transport and separation of superparamagnetic (SPM) beads, based on a travelling magnetic field wave generated by the combination of a micromagnet array (MMA) and an applied rotating magnetic field. Here, we present two novel MMA designs that allow SPM beads to be focused, sorted, and separated on-chip. Converging MMAs were used to rapidly collect the SPM beads from a large region of the chip and focus them into synchronized lines. We characterise the collection efficiency of the devices and demonstrate that they can facilitate on-chip analysis of populations of SPM beads using a single-point optical detector. The diverging MMAs were used to control the transport of the beads and to separate them based on their size. The separation efficiency of these devices was determined by the orientation of the magnetisation of the micromagnets relative to the external magnetic field and the size of the beads relative to that of micromagnets. By controlling these parameters and the rotation of the external magnetic field we demonstrated the controlled transport of SPM bead-labelled single MDA-MB-231 cells. The use of these novel MMAs promises to allow magnetically-labelled cells to be efficiently isolated and then manipulated on-chip for analysis with high-resolution chemical and physical techniques.
      377Scopus© Citations 9