Single-Domain Multiferroic Array-Addressable Terfenol-D (SMArT) Micromagnets for Programmable Single-Cell Capture and Release.

Programming magnetic fields with microscale control can enable automation at the scale of single cells ≈10 µm. Most magnetic materials provide a consistent magnetic field over time but the direction or field strength at the microscale is not easily modulated. However, magnetostrictive materials, when coupled with ferroelectric material (i.e., strain-mediated multiferroics), can undergo magnetization reorientation due to voltage-induced strain, promising refined control of magnetization at the micrometer-scale. This work demonstrates the largest single-domain microstructures (20 µm) of Terfenol-D (Tb0.3 Dy0.7 Fe1.92 ), a material that has the highest magnetostrictive strain of any known soft magnetoelastic material. These Terfenol-D microstructures enable controlled localization of magnetic beads with sub-micrometer precision. Magnetically labeled cells are captured by the field gradients generated from the single-domain microstructures without an external magnetic field. The magnetic state on these microstructures is switched through voltage-induced strain, as a result of the strain-mediated converse magnetoelectric effect, to release individual cells using a multiferroic approach. These electronically addressable micromagnets pave the way for parallelized multiferroics-based single-cell sorting under digital control for biotechnology applications.

Capturing magnetic bead-based arrays using perpendicular magnetic anisotropy.

Designing and implementing means of locally trapping magnetic beads and understanding the factors underlying the bead capture force are important steps toward advancing the capture-release process of magnetic particles for biological applications. In particular, capturing magnetically labeled cells using magnetic microstructures with perpendicular magnetic anisotropy (PMA) will enable an approach to cell manipulation for emerging lab-on-a-chip devices. Here, a Co (0.2 nm)/Ni (0.4 nm) multilayered structure was designed to exhibit strong PMA and large saturation magnetization (M s ). Finite element simulations were performed to assess the dependence of the capture force on the value of M s . The simulated force profile indicated the largest force at the perimeter of the disks. Arrays of Co/Ni disk structures of (4-7) µm diameter were fabricated and tested in a microchannel with suspended fluorescent magnetic beads. The magnetic beads were captured and localized to the edge of the disks as predicted by the simulations. This approach has been demonstrated to enable uniform assembly of magnetic beads without external fields and may provide a pathway toward precise cell manipulation methods.

Size-tunable microvortex capture of rare cells.

Inertial separation of particles and cells based on their size has advanced significantly over the last decade. However, size-based inertial separation methods require precise tuning of microfluidic device geometries to adjust the separation size of particles or cells. Here, we show a passive capture method that targets a wide size range of cells by controlling the flow conditions in a single device geometry. This multimodal capture device is designed to generate laminar vortices in lateral cavities that branch from long rectangular channels. Micro-vortices generated at lower Reynolds numbers capture and stabilize large particles in equilibrium orbits or limit cycles near the vortex core. Other smaller particles or cells orbit near the vortex boundaries and they are susceptible to exiting the cavity flow. In the same cavity, however, at higher Reynolds number, we observe small particles migrating inward. This evolution in limit cycle trajectories led to a corresponding evolution in the average size of captured particles, indicating that the outermost orbits are less stable. We identify three phases of capture as a function of Reynolds number that give rise to unique particle orbit trajectories. Flow-based switching overcomes a major engineering challenge to automate capture and release of polydisperse cell subpopulations. The approach can expand clinical applications of label free trapping in isolating and processing a larger subset of rare cells like circulating tumor cells (CTCs) from blood and other body fluids.

Research highlights: microfluidic-enabled single-cell epigenetics.

Individual cells are the fundamental unit of life with diverse functions from metabolism to motility. In multicellular organisms, a single genome can give rise to tremendous variability across tissues at the single-cell level due to epigenetic differences in the genes that are expressed. Signals from the local environment or a history of signals can drive these variations, and tissues have many cell types that play separate roles. This epigenetic heterogeneity is of biological importance in normal functions such as tissue morphogenesis and can contribute to development or resistance of cancer, or other disease states. Therefore, an improved understanding of variations at the single cell level are fundamental to understanding biology and developing new approaches to combating disease. Traditional approaches to characterize epigenetic modifications of chromatin or the transcriptome of cells have often focused on blended responses of many cells in a tissue; however, such bulk measures lose spatial and temporal differences that occur from cell to cell, and cannot uncover novel or rare populations of cells. Here we highlight a flurry of recent activity to identify the mRNA profiles from thousands of single-cells as well as chromatin accessibility and histone marks on single to few hundreds of cells. Microfluidics and microfabrication have played a central role in the range of new techniques, and will likely continue to impact their further development towards routine single-cell epigenetic analysis.