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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