Magnetic Lateral Ladder for Unidirectional Transport of Microrobots: Design Principles and Potential Applications of Cells-on-Chip.

Functionalized microrobots, which are directionally manipulated in a controlled and precise manner for specific tasks, face challenges. However, magnetic field-based controls constrain all microrobots to move in a coordinated manner, limiting their functions and independent behaviors. This article presents a design principle for achieving unidirectional microrobot transport using an asymmetric magnetic texture in the shape of a lateral ladder, which the authors call the "railway track." An asymmetric magnetic energy distribution along the axis allows for the continuous movement of microrobots in a fixed direction regardless of the direction of the magnetic field rotation. The authors demonstrated precise control and simple utilization of this method. Specifically, by placing magnetic textures with different directionalities, an integrated cell/particle collector can collect microrobots distributed in a large area and move them along a complex trajectory to a predetermined location.  The authors can leverage the versatile capabilities offered by this texture concept, including hierarchical isolation, switchable collection, programmable pairing, selective drug-response test, and local fluid mixing for target objects. The results demonstrate the importance of microrobot directionality in achieving complex individual control. This novel concept represents significant advancement over conventional magnetic field-based control technology and paves the way for further research in biofunctionalized microrobotics.

Operational Parameters for Sub-Nano Tesla Field Resolution of PHMR Sensors in Harsh Environments.

The resolution of planar-Hall magnetoresistive (PHMR) sensors was investigated in the frequency range from 0.5 Hz to 200 Hz in terms of its sensitivity, average noise level, and detectivity. Analysis of the sensor sensitivity and voltage noise response was performed by varying operational parameters such as sensor geometrical architectures, sensor configurations, sensing currents, and temperature. All the measurements of PHMR sensors were carried out under both constant current (CC) and constant voltage (CV) modes. In the present study, Barkhausen noise was revealed in 1/f noise component and found less significant in the PHMR sensor configuration. Under measured noise spectral density at optimized conditions, the best magnetic field detectivity was achieved better than 550 pT/√Hz at 100 Hz and close to 1.1 nT/√Hz at 10 Hz for a tri-layer multi-ring PHMR sensor in an unshielded environment. Furthermore, the promising feasibility and possible routes for further improvement of the sensor resolution are discussed.

Bridge Resistance Compensation for Noise Reduction in a Self-Balanced PHMR Sensor.

Advanced microelectromechanical system (MEMS) magnetic field sensor applications demand ultra-high detectivity down to the low magnetic fields. To enhance the detection limit of the magnetic sensor, a resistance compensator integrated self-balanced bridge type sensor was devised for low-frequency noise reduction in the frequency range of 0.5 Hz to 200 Hz. The self-balanced bridge sensor was a NiFe (10 nm)/IrMn (10 nm) bilayer structure in the framework of planar Hall magnetoresistance (PHMR) technology. The proposed resistance compensator integrated with a self-bridge sensor architecture presented a compact and cheaper alternative to marketable MEMS MR sensors, adjusting the offset voltage compensation at the wafer level, and led to substantial improvement in the sensor noise level. Moreover, the sensor noise components of electronic and magnetic origin were identified by measuring the sensor noise spectral density as a function of temperature and operating power. The lowest achievable noise in this device architecture was estimated at ~3.34 nV/Hz at 100 Hz.

Multifarious Transit Gates for Programmable Delivery of Bio-functionalized Matters.

Programmable delivery of biological matter is indispensable for the massive arrays of individual objects in biochemical and biomedical applications. Although a digital manipulation of single cells has been implemented by the integrated circuits of micromagnetophoretic patterns with current wires, the complex fabrication process and multiple current operation steps restrict its practical application for biomolecule arrays. Here, a convenient approach using multifarious transit gates is proposed, for digital manipulation of biofunctionalized microrobotic particles that can pass through the local energy barriers by a time-dependent pulsed magnetic field instead of multiple current wires. The multifarious transit gates including return, delay, and resistance linear gates, as well as dividing, reversed, and rectifying T-junction gates, are investigated theoretically and experimentally for the programmable manipulation of microrobotic particles. The results demonstrate that, a suitable angle of the gating field at a suitable time zone is crucial to implement digital operations at integrated multifarious transit gates along bifurcation paths to trap microrobotic particles in specific apartments, paving the way for flexible on-chip arrays of biomolecules and cells.

Autonomous Magnetic Microrobots by Navigating Gates for Multiple Biomolecules Delivery.

The precise delivery of biofunctionalized matters is of great interest from the fundamental and applied viewpoints. In spite of significant progress achieved during the last decade, a parallel and automated isolation and manipulation of rare analyte, and their simultaneous on-chip separation and trapping, still remain challenging. Here, a universal micromagnet junction for self-navigating gates of microrobotic particles to deliver the biomolecules to specific sites using a remote magnetic field is described. In the proposed concept, the nonmagnetic gap between the lithographically defined donor and acceptor micromagnets creates a crucial energy barrier to restrict particle gating. It is shown that by carefully designing the geometry of the junctions, it becomes possible to deliver multiple protein-functionalized carriers in high resolution, as well as MCF-7 and THP-1 cells from the mixture, with high fidelity and trap them in individual apartments. Integration of such junctions with magnetophoretic circuitry elements could lead to novel platforms without retrieving for the synchronous digital manipulation of particles/biomolecules in microfluidic multiplex arrays for next-generation biochips.

Magnetically Selective Versatile Transport of Microrobotic Carriers.

Field-driven transport systems offer great promise for use as biofunctionalized carriers in microrobotics, biomedicine, and cell delivery applications. Despite the construction of artificial microtubules using several micromagnets, which provide a promising transport pathway for the synchronous delivery of microrobotic carriers to the targeted location inside microvascular networks, the selective transport of different microrobotic carriers remains an unexplored challenge. This study demonstrated the selective manipulation and transport of microrobotics along a patterned micromagnet using applied magnetic fields. Owing to varied field strengths, the magnetic beads used as the microrobotic carriers with different sizes revealed varied locomotion, including all of them moving along the same direction, selective rotation, bidirectional locomotion, and all of them moving in a reversed direction. Furthermore, cells immobilized with magnetic beads and nanoparticles also revealed varied locomotion. It is expected that such steering strategies of microrobotic carriers can be used in microvascular channels for the targeted delivery of drugs or cells in an organized manner.

Magnetophoretic Micro-Distributor for Controlled Clustering of Cells.

Cell clustering techniques are important to produce artificial cell clusters for in vitro models of intercellular mechanisms at the single-cell level. The analyses considering physical variables such as the shape and size of cells have been very limited. In addition, the precise manipulation of cells and control of the physical variables are still challenging. In this paper, a magnetophoretic device consisting of a trampoline micromagnet and active elements that enable the control of individual selective jumping motion and positioning of a micro-object is proposed. Based on a numerical simulation under various conditions, automatic separation or selective clustering of micro-objects according to their sizes is performed by parallel control and programmable manipulation. This method provides efficient control of the physical variables of cells and grouping of cells with the desired size and number, which can be a milestone for a better understanding of the intercellular dynamics between clustered cells at the single-cell level for future cell-on-chip applications.

Tailoring matter orbitals mediated using a nanoscale topographic interface for versatile colloidal current devices.

Conventional micro-particle manipulation technologies have been used for various biomedical applications using dynamics on a plane without vertical movement. In this case, irregular topographic structures on surfaces could be a factor that causes the failure of the intended control. Here, we demonstrated a novel colloidal particle manipulation mediated by the topographic effect generated by the "micro hill" and "surface gradient" around a micro-magnet. The magnetic landscape, matter orbital, created by periodically arranged circular micro-magnets, induces a symmetric orbit of magnetic particle flow under a rotating magnetic field. The topographic effect can break this symmetry of the energy distribution by controlling the distance between the source of the driving force and target particles by several nanometers on the surface morphology. The origin symmetric orbit of colloidal flow can be distorted by modifying the symmetry in the energy landscape at the switching point without changing the driving force. The enhancement of the magnetic effect of the micro-magnet array can lead to the recovery of the symmetry of the orbit. Also, this effect on the surfaces of on-chip-based devices configured by symmetry control was demonstrated for selective manipulation, trapping, recovery, and altering the direction using a time-dependent magnetic field. Hence, the developed technique could be used in various precise lab-on-a-chip applications, including where the topographic effect is required as an additional variable without affecting the existing control method.

Magnetophoretic Decoupler for Disaggregation and Interparticle Distance Control.

The manipulation of superparamagnetic beads has attracted various lab on a chip and magnetic tweezer platforms for separating, sorting, and labeling cells and bioentities, but the irreversible aggregation of beads owing to magnetic interactions has limited its actual functionality. Here, an efficient solution is developed for the disaggregation of magnetic beads and interparticle distance control with a magnetophoretic decoupler using an external rotating magnetic field. A unique magnetic potential energy distribution in the form of an asymmetric magnetic thin film around the gap is created and tuned in a controlled manner, regulated by the size ratio of the bead with a magnetic pattern. Hence, the aggregated beads are detached into single beads and transported in one direction in an array pattern. Furthermore, the simultaneous and accurate spacing control of multiple magnetic bead pairs is performed by adjusting the angle of the rotating magnetic field, which continuously changes the energy well associated with a specific shape of the magnetic patterns. This technique offers an advanced solution for the disaggregation and controlled manipulation of beads, can allow new possibilities for the enhanced functioning of lab on a chip and magnetic tweezers platforms for biological assays, intercellular interactions, and magnetic biochip systems.

Mattertronics for programmable manipulation and multiplex storage of pseudo-diamagnetic holes and label-free cells.

Manipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms.

Magnetically Characterized Molecular Lubrication between Biofunctionalized Surfaces.

We demonstrate an efficient approach for quantifying frictional forces (sub-piconewton) at nano-bio interfaces by controlled magnetic forces, which is based on simultaneous measurements of critical frequencies for streptavidin-coupled magnetic particles. The maximum phase angle, being corresponded with the critical frequency, is formulated in terms of magnetic, frictional, and viscous forces of the particles on DNA- and SiO2-functionalized micromagnet arrays. The streptavidin/DNA interface shows lower friction as an enhanced lubrication than the streptavidin/SiO2 interface, which is indicated by the lower transition field of quasi-static motion, the larger ratio of dynamic particles, and also the higher velocity of the particles. The friction coefficients at the streptavidin/DNA and streptavidin/SiO2 interfaces are evaluated numerically as 0.07 and 0.11, respectively, regardless of the vertical force and the velocity. The proposed method would open up new possibilities to study mechanical interactions at biological surfaces.

An on-chip micromagnet frictionometer based on magnetically driven colloids for nano-bio interfaces.

A novel method based on remotely controlled magnetic forces of bio-functionalized superparamagnetic colloids using micromagnet arrays was devised to measure frictional force at the sub-picoNewton (pN) scale for bio-nano-/micro-electromechanical system (bio-NEMS/MEMS) interfaces in liquid. The circumferential motion of the colloids with phase-locked angles around the periphery of the micromagnets under an in-plane rotating magnetic field was governed by a balance between tangential magnetic force and drag force, which consists of viscous and frictional forces. A model correlating the phase-locked angles of the steady colloid rotation was formulated and validated by measuring the angles under controlled magnetic forces. Hence, the frictional forces on the streptavidin/Teflon interface between the colloids and the micromagnet arrays were obtained using the magnetic forces at the phase-locked angles. The friction coefficient for the streptavidin/Teflon interface was estimated to be approximately 0.036 regardless of both vertical force in the range of a few hundred pN and velocity in the range of a few tenths of µm s(-1).

Dynamic trajectory analysis of superparamagnetic beads driven by on-chip micromagnets.

We investigate the non-linear dynamics of superparamagnetic beads moving around the periphery of patterned magnetic disks in the presence of an in-plane rotating magnetic field. Three different dynamical regimes are observed in experiments, including (1) phase-locked motion at low driving frequencies, (2) phase-slipping motion above the first critical frequency fc1, and (3) phase-insulated motion above the second critical frequency fc2. Experiments with Janus particles were used to confirm that the beads move by sliding rather than rolling. The rest of the experiments were conducted on spherical, isotropic magnetic beads, in which automated particle position tracking algorithms were used to analyze the bead dynamics. Experimental results in the phase-locked and phase-slipping regimes correlate well with numerical simulations. Additional assumptions are required to predict the onset of the phase-insulated regime, in which the beads are trapped in closed orbits; however, the origin of the phase-insulated state appears to result from local magnetization defects. These results indicate that these three dynamical states are universal properties of bead motion in non-uniform oscillators.

Magnetophoretic circuits for digital control of single particles and cells.

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.