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. O ne of the main goals of lab-on-a-chip research is to develop generic platforms for manipulating small fluid droplets, colloidal particles and single cells with the flexibility, scalability and automation of modern-day computer circuits. Single-cell arrays represent one high impact application of lab-on-a-chip tools, which are increasingly being adopted to evaluate rare biological responses in small-cell subsets that are overlooked by the ensemble averaging approaches of traditional biology. Improved understanding of these rare cellular responses can profoundly impact the development of vaccines and pharmaceuticals for curing infectious diseases and cancer 1,2 ; however there are few existing techniques with the scale and flexibility to unmask single-cell heterogeneity and pave the way for new medical breakthroughs 3-7 .In particular, there is an urgent need for tools to organize large arrays of single cells and single-cell pairs, evaluate the temporal responses of individual cell and cell-pair interactions over long durations, and retrieve specific cells from the array for follow-on analyses. 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 8-11 , optic 12-18 , 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.Our approach has significant similarities with magnetic bubble memory technology 37 , which was originally developed to store memory and implement lo...

Small-scale magnetic soft-bodied robots based on biocompatible and biodegradable materials are essential for their potential high-impact minimally invasive medical applications inside the human body. Therefore, a strategy for fully biodegradable untethered soft millirobots with encoded 3D magnetic anisotropy for their static or dynamic shape programming is presented. Such a robot body is comprised of a porcine extracellular matrix-derived collagenbased hydrogel network with embedded superparamagnetic iron oxide nanoparticles (SPIONs). 3D magnetization programming inside the hydrogel body is achieved by directionally self-assembled SPION chains using an external permanent magnet. As a proof-of-concept demonstration, a hydrogel milligripper that can undergo flexible and reversible shape deformations inside glycerol and biologically relevant liquid media is presented. The gripper can perform cargo grabbing, transportation by rolling, and release by controlling magnetic field inputs. These milli-grippers can be completely degraded by the matrix metalloproteinase-2 enzyme in physiologically relevant concentrations. Furthermore, biocompatibility tests using human umbilical cord vein endothelial cells with the degradation products of the grippers demonstrate no acute toxicity. The approach offers a facile fabrication strategy for designing biocompatible and biodegradable soft robots using nanocomposite materials with programmable 3D magnetic anisotropy toward future medical applications.

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thermia, and embolization, at the target location. [9,10] Recently, also soft-bodied wireless medical robots have become possible, where soft body enables programmable shape change, multifunctionality, and reconfiguration and safe operation inside the body. [11][12][13][14][15] Efforts have been made to develop and implement such robots, including fabrication of microscale soft robotic devices, and synthesis of biocompatible or biodegradable materials and strategies for locomotion inside the body. [16][17][18][19] However, applying these approaches have many limitations to operate safely and robustly in such complicated environments.Among various limitations, achieving strong adhesion to biological tissues whose surfaces are soft, rough, and wet is critical for the robots to efficiently implement various biomedical functions, including collecting bio-signals, bonding with unwanted derivatives and destroying them, healing wounds, and applying electrical impulses to nerves. [20][21][22][23] Although there are already commercial adhesives for tissues, the lack of long-term durability causes the failure of adhesion on the tissue. [24,25] Tough adhesives made of double-layered hydrogels [24][25][26] and dry double-sided tapes [27] were recently suggested for biological adhesives. These tissue adhesives are capable of strong adhesion to wet tissues, it is very difficult to detach them, indicating that a surgical operation is required for the detachment process. In addition, uncontrolled detachment can cause not only a problem of leaving an undesirable residue in Recently, the realization of minimally invasive medical interventions on targeted tissues using wireless small-scale medical robots has received an increasing attention. For effective implementation, such robots should have a strong adhesion capability to biological tissues and at the same time easy controlled detachment should be possible, which has been challenging. To address such issue, a small-scale soft robot with octopus-inspired hydrogel adhesive (OHA) is proposed. Hydrogels of different Young's moduli are adapted to achieve a biocompatible adhesive with strong wet adhesion by preventing the collapse of the octopus-inspired patterns during preloading. Introduction of poly(N-isopropylacrylamide) hydrogel for dome-like protuberance structure inside the sucker wall of polyethylene glycol diacrylate hydrogel provides a strong tissue attachment in underwater and at the same time enables easy detachment by temperature changes due to its temperature-dependent volume change property. It is finally demonstrated that the small-scale soft OHA robot can efficiently implement biomedical functions owing to strong adhesion and controllable detachment on biological tissues while operating inside the body. Such robots with repeatable tissue attachment and detachment possibility pave the way for future wireless soft miniature robots with minimally invasive medical interventions.

Soft untethered micromachines with overall sizes less than 100 μm enable diverse programmed shape transformations and functions for future biomedical and organ-on-a-chip applications. However, fabrication of such machines has been hampered by the lack of control of microactuator’s programmability. To address such challenge, we use two-photon polymerization to selectively link Janus microparticle-based magnetic microactuators by three-dimensional (3D) printing of soft or rigid polymer microstructures or links. Sequentially, we position each microactuator at a desired location by surface rolling and rotation to a desired position and orientation by applying magnetic field–based torques, and then 3D printing soft or rigid links to connect with other temporarily fixed microactuators. The linked 2D microactuator networks exhibit programmed 2D and 3D shape transformations, and untethered limbless and limbed micromachine prototypes exhibit various robotic gaits for surface locomotion. The fabrication strategy presented here can enable soft micromachine designs and applications at the cellular scales.

A lab-on-a-chip (LOC) magnetophoretic system for the remotely controllable transport of magnetic particles actuated by thin permalloy magnetic tracks has been developed as a novel architecture composed of radii and spiral tracks resembling a spider web network, where the network tracks have the asymmetric and anisotropic magnetic properties for the directional transportation of particles (cargos). A planar Hall resistance (PHR) sensor is integrated with the web networks, and the manipulation and detection are achieved via superparamagnetic particles with dual functions as a biomolecule cargo for transportation and labels for monitoring. The streptavidin protein-coated magnetic particles are precisely manipulated toward the PHR sensor surface via the radii and spiral tracks by applying an external rotating magnetic field. The stray field was analyzed in terms of the particle coverage on the sensor surface, where the sensor signal linearly varies with the number of particles on the sensor surface. This allows the effective collection of low-density biomolecule carriers to one specific point and monitors the accumulated carriers. The developed novel technology could affect multiple fields, including bioassays, cell manipulation and separation and biomechanics.

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).

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