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.     

On‐Chip Magnetic Platform for Single‐Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated.     

Fabrication of precisely controlled silicon wire and cone arrays by electrochemical etching

There is an exponentially growing need for well-oriented, vertical silicon nano/micro-structure arrays, particularly in high-density integrated electronic devices. Here, we demonstrate that precisely controlled vertical arrays of silicon wires and cones can be fabricated by a combined treatment strategy of electrochemical and chemical etchings. First, a periodically ordered array of silicon wires was readily fabricated at microscale by simple electrochemical etching in which the current density played a critical role in determining the wire diameter and interspacing. The microstructures fabricated by electrochemical etching were more precisely tuned by further chemical etching, thereby transforming into cone arrays with extremely sharp tips where the cone height was controlled by the etching time. This approach could have broad utility in many electronics requiring miniaturization and high-density integration such as field emitters, photovoltaic and thermoelectric devices.     

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single‐step process using 2‐photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high‐dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real‐time force‐sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated.     

Polycrystalline diamond UV-triggered MESFET receivers

Optically triggered UV sensitive receivers were fabricated on polycrystalline diamond as surface channel MESFETs. Opaque gates with asymmetric structure were designed in order to improve charge photogeneration mainly within the gate-drain region. Photogenerated holes contributed to the channel charge by assistance of the local electric field, in such a way improving the current signal at the drain contact. The sensitivity to UV light is demonstrated by using 3?ns wide laser pulses at 193?nm, well over the diamond bandgap. The receiver transient response to such laser pulses shows that the photogeneration process is only limited by the pulse rise time and charge collection at the drain contact completed in a time scale of a few nanoseconds. Such opaque gate three-terminal devices are suitable for application in emerging photonic technologies, for power-management system optical receivers, where copper wires and EM shielding can be replaced by lightweight optical fibers.     

Thermodynamic behavior of molecular-scale quantum-dot cellular automata (QCA) wires and logic devices

Quantum-dot cellular automata (QCA) offers a new paradigm for molecular electronics, a paradigm in which information transmission and processing depend on electrostatic interactions between charges in arrays of cells composed of quantum dots. Fundamental questions about the operational temperature and functional gain of devices built from molecular-scale QCA cells are addressed in this paper through a statistical-mechanical model based on electrostatic interactions. The model provides exact solutions for the thermodynamic constraints on operation of small arrays of cells (up to 15). An Ising approximation dramatically reduces the computational task and allows modeling of the thermodynamic behavior of semi-infinite QCA wires. The probability of getting the correct output from a QCA device for a given input depends on temperature, cell size, cell-cell distance, effective dielectric constant of the medium, and the number of cells in the array. Using parameters derived from molecular candidates for QCA cells, the statistical-mechanical model predicts that majority gates should give correct output at temperatures of up to 450 K, while wires of thousands to millions of QCA cells are predicted to operate as functional devices at room temperature.     

A generic automated/semiautomated digital multi-electrodeinstrument for field resistivity measurements

The objective of this work is to design and test a digital multi-electrode acquisition system for use in geophysical investigations utilizing direct current electrical (geoelectric) methods. The system is a 64-electrode modular system, which utilizes field electrodes with individual wires that lead back to a digital switch box and then to a data acquisition instrument (Iris Syscal R2). The electronic design allows for different arrays or geometrical switching configurations of the field electrodes in order to allow for rapid data reading and yield essentially real-time results. Additionally, the electronic switch box has the capability to be connected in series to similar switch boxes and, therefore, has the ability to switch between an unlimited number of electrodes. The acquisition control software, developed as an interface for the hardware, controls operation of both the digital switch box and the resistivity acquisition instrument     

Memristor‐Based Analog Computation and Neural Network Classification with a Dot Product Engine

Using memristor crossbar arrays to accelerate computations is a promising approach to efficiently implement algorithms in deep neural networks. Early demonstrations, however, are limited to simulations or small‐scale problems primarily due to materials and device challenges that limit the size of the memristor crossbar arrays that can be reliably programmed to stable and analog values, which is the focus of the current work. High‐precision analog tuning and control of memristor cells across a 128 × 64 array is demonstrated, and the resulting vector matrix multiplication (VMM) computing precision is evaluated. Single‐layer neural network inference is performed in these arrays, and the performance compared to a digital approach is assessed. Memristor computing system used here reaches a VMM accuracy equivalent of 6 bits, and an 89.9% recognition accuracy is achieved for the 10k MNIST handwritten digit test set. Forecasts show that with integrated (on chip) and scaled memristors, a computational efficiency greater than 100 trillion operations per second per Watt is possible.     

Plasmonics—A Route to Nanoscale Optical Devices

The further integration of optical devices will require the fabrication of waveguides for electromagnetic energy below the diffraction limit of light. We investigate the possibility of using arrays of closely spaced metal nanoparticles for this purpose. Coupling between adjacent particles sets up coupled plasmon modes that give rise to coherent propagation of energy along the array. A point dipole analysis predicts group velocities of energy transport that exceed 0.1c along straight arrays and shows that energy transmission and switching through chain networks such as corners (see Figure) and tee structures is possible at high efficiencies. Radiation losses into the far field are expected to be negligible due to the near‐field nature of the coupling, and resistive heating leads to transmission losses of about 6 dB/μm for gold and silver particles. We analyze macroscopic analogues operating in the microwave regime consisting of closely spaced metal rods by experiments and full field electrodynamic simulations. The guiding structures show a high confinement of the electromagnetic energy and allow for highly variable geometries and switching. Also, we have fabricated gold nanoparticle arrays using electron beam lithography and atomic force microscopy manipulation. These plasmon waveguides and switches could be the smallest devices with optical functionality.     

Biosensing by Densely Packed and Optically Coupled Plasmonic Particle Arrays

Densely packed plasmonic particle arrays are investigated for biosensing applications. Such particle arrays exhibit interparticle optical coupling creating a strong field between the particles, which is useful for sensing purposes. The sensor properties, such as bulk sensitivity, layer sensitivity, and the depth of sensitivity are investigated with the aid of a multiple multipole program. Sensitivity to the analyte with low concentration is also examined by a dynamic adsorption processes. The detectable concentration limit of streptavidin within 3000 s in the detection system is expected from the signal‐to‐noise to be less than 150 pM .     

A Microfabricated Sandwiching Assay for Nanoliter and High‐Throughput Biomarker Screening

Cells secrete substances that are essential to the understanding of numerous immunological phenomena and are extensively used in clinical diagnoses. Countless techniques for screening of biomarker secretion in living cells have generated valuable information on cell function and physiology, but low volume and real‐time analysis is a bottleneck for a range of approaches. Here, a simple, highly sensitive assay using a high‐throughput micropillar and microwell array chip (MIMIC) platform is presented for monitoring of biomarkers secreted by cancer cells. The sensing element is a micropillar array that uses the enzyme‐linked immunosorbent assay (ELISA) mechanism to detect captured biomolecules. When integrated with a microwell array where few cells are localized, interleukin 8 (IL‐8) secretion can be monitored with nanoliter volume using multiple micropillar arrays. The trend of cell secretions measured using MIMICs matches the results from conventional ELISA well while it requires orders of magnitude less cells and volumes. Moreover, the proposed MIMIC is examined to be used as a drug screening platform by delivering drugs using micropillar arrays in combination with a microfluidic system and then detecting biomolecules from cells as exposed to drugs.     

Three‐Dimensional Exploration and Mechano‐Biophysical Analysis of the Inner Structure of Living Cells

A novel mechanobiological method is presented to explore qualitatively and quantitatively the inside of living biological cells in three dimensions, paving the way to sense intracellular changes during dynamic cellular processes. For this purpose, holographic optical tweezers, which allow the versatile manipulation of nanoscopic and microscopic particles by means of tailored light fields, are combined with self‐interference digital holographic microscopy. This biophotonic holographic workstation enables non‐contact, minimally invasive, flexible, high‐precision optical manipulation and accurate 3D tracking of probe particles that are incorporated by phagocytosis in cells, while simultaneously quantitatively phase imaging the cell morphology. In a first model experiment, internalized polystyrene microspheres with 1 μm diameter are three‐dimensionally moved and tracked in order to quantify distances within the intracellular volume with submicrometer accuracy. Results from investigations on cell swelling provoked by osmotic stimulation demonstrate the homogeneous stretching of the cytoskeleton network, and thus that the proposed method provides a new way for the quantitative 3D analysis of the dynamic intracellular morphology.     

Local Particle Mean Velocity Measurement in Pneumatic Conveying Pipelines Using Electrostatic Sensor Arrays

In this paper, a measurement system for the local mean velocity of pneumatically conveyed particles is proposed and developed. It mainly consists of electrostatic sensor arrays, signal conditioning circuits, and a digital signal processor (DSP)-based data acquisition and processing unit. Electrostatic sensor arrays are used to detect the charge on particles in its sensing zone and further make the local particle mean velocity measurement in conjunction with cross-correlation method. The sampling frequency is determined from theoretical analysis of the bandwidth of electrostatic signal and accuracy of correlation velocity calculation. Experiments are carried out on a belt conveyor and a gravity-fed particle rig to determine the optimized sampling number of the electrostatic signal through analyzing the measurement error of the transit time. The results showed that the more sampling numbers, the higher stability of measurement results. The repeatability of the measurement system is less than ±2.2% and the linearity is better than ±4.9% over the velocity range of 5.50–21.98 m/s. Experiments are also performed on a high-pressure dense-phase pneumatic conveying system of pulverized coal, indicating that the measurement system is capable of achieving local mean velocity measurement of pneumatically conveyed particles with the relative standard deviation less than 5.5%.     

Phonon‐Assisted Electro‐Optical Switches and Logic Gates Based on Semiconductor Nanostructures

High‐performance nanostructured electro‐optical switches and logic gates are highly desirable as essential building blocks in integrated photonics. In contrast to silicon‐based optoelectronic devices, with their inherent indirect optical bandgap, weak light‐modulation mechanism, and sophisticated device configuration, direct‐bandgap‐semiconductor nanostructures with attractive electro‐optical properties are promising candidates for the construction of nanoscale optical switches for on‐chip photonic integrations. However, previously reported semiconductor‐nanostructure optical switches suffer from serious drawbacks such as high drive voltage, limited operation spectral range, and low modulation depth. High‐efficiency electro‐optical switches based on single CdS nanobelts with low drive voltage, ultra‐high on/off ratio, and broad operation wavelength range, properties resulting from unique electric‐field‐dependent phonon‐assisted optical transitions, are demonstrated. Furthermore, functional NOT, NOR, and NAND optical logic gates are demonstrated based on these switches. These switches and optical logic gates represent an important step toward integrated photonic circuits.     

Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high‐force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi‐analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti‐epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof‐of‐concept, EpCAM‐labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.     

Nondestructive Real‐Time Monitoring of Enhanced Stem Cell Differentiation Using a Graphene‐Au Hybrid Nanoelectrode Array

Stem cells have attracted increasing research interest in the field of regenerative medicine because of their unique ability to differentiate into multiple cell lineages. However, controlling stem cell differentiation efficiently and improving the current destructive characterization methods for monitoring stem cell differentiation are the critical issues. To this end, multifunctional graphene–gold (Au) hybrid nanoelectrode arrays (NEAs) to: (i) investigate the effects of combinatorial physicochemical cues on stem cell differentiation, (ii) enhance stem cell differentiation efficiency through biophysical cues, and (iii) characterize stem cell differentiation in a nondestructive real‐time manner are developed. Through the synergistic effects of physiochemical properties of graphene and biophysical cues from nanoarrays, the graphene‐Au hybrid NEAs facilitate highly enhanced cell adhesion and spreading behaviors. In addition, by varying the dimensions of the graphene‐Au hybrid NEAs, improved stem cell differentiation efficiency, resulting from the increased focal adhesion signal, is shown. Furthermore, graphene‐Au hybrid NEAs are utilized to monitor osteogenic differentiation of stem cells electrochemically in a nondestructive real‐time manner. Collectively, it is believed the unique multifunctional graphene‐Au hybrid NEAs can significantly advance stem‐cell‐based biomedical applications.     

Synergistic Modulation of Surface Interaction to Assemble Metal Nanoparticles into Two‐Dimensional Arrays with Tunable Plasmonic Properties

A simple strategy based on the synergistic modulation of inter‐particle and substrate‐particle interaction is applied for the large‐scale fabrication of two‐dimensional (2D) Au and Ag nanoparticle arrays. The surface charge of the substrate is used to redistribute the double layer electric charges on the particles and to modulate the inter‐particle distance within the 2D nanoparticle arrays on the substrate. The resultant arrays, with a wide range of inter‐particle distances, display tunable plasmonic properties. It can be foreseen that such 2D nanoparticle arrays possess potential applications as multiplexed colorimetric sensors, integrated devices and antennas. Herein, it is demonstrated that these arrays can be employed as wavelength‐selective substrates for multiplexed acquisition of surface‐enhanced Raman scattering (SERS) spectra. This simple one step process provides an attractive and low cost strategy to produce high quality and large area 2D ordered arrays with tunable properties.     

Array-controlled ultrasonic manipulation of particles in planar acoustic resonator

Ultrasonic particle manipulation tools have many promising applications in life sciences, expanding on the capabilities of current manipulation technologies. In this paper, the ultrasonic manipulation of particles and cells along a microfluidic channel with a piezoelectric array is demonstrated. An array integrated into a planar multilayer resonator structure drives particles toward the pressure nodal plane along the centerline of the channel, then toward the acoustic velocity maximum centered above the subset of elements that are active. Switching the active elements along the array moves trapped particles along the microfluidic channel. A 12-element 1-D array coupled to a rectangular capillary has been modeled and fabricated for experimental testing. The device has a 300-μm-thick channel for a half-wavelength resonance near 2.5 MHz, with 500 μm element pitch. Simulation and experiment confirm the expected trapping of particles at the center of the channel and above the set of active elements. Experiments demonstrated the feasibility of controlling the position of particles along the length of the channel by switching the active array elements.     

Drug delivery: Magnetic Luminescent Porous Silicon Microparticles for Localized Delivery of Molecular Drug Payloads (Small 22/2010)

Magnetic manipulation, fluorescent tracking, and localized delivery of a drug payload to cancer cells in vitro is demonstrated, using nanostructured porous silicon microparticles as a carrier. The multifunctional microparticles are prepared by electrochemical porosification of a silicon wafer in a hydrofluoric acid‐containing electrolyte, followed by removal and fracture of the porous layer into particles using ultrasound. The intrinsically luminescent particles are loaded with superparamagnetic iron oxide nanoparticles and the anti‐cancer drug doxorubicin. The drug‐containing particles are delivered to human cervical cancer (HeLa) cells in vitro, under the guidance of a magnetic field. The high concentration of particles in the proximity of the magnetic field results in a high concentration of drug being released in that region of the Petri dish, and localized cell death is confirmed by cellular viability assay (Calcein AM).     

Magnetic Luminescent Porous Silicon Microparticles for Localized Delivery of Molecular Drug Payloads

Magnetic manipulation, fluorescent tracking, and localized delivery of a drug payload to cancer cells in vitro is demonstrated, using nanostructured porous silicon microparticles as a carrier. The multifunctional microparticles are prepared by electrochemical porosification of a silicon wafer in a hydrofluoric acid‐containing electrolyte, followed by removal and fracture of the porous layer into particles using ultrasound. The intrinsically luminescent particles are loaded with superparamagnetic iron oxide nanoparticles and the anti‐cancer drug doxorubicin. The drug‐containing particles are delivered to human cervical cancer (HeLa) cells in vitro, under the guidance of a magnetic field. The high concentration of particles in the proximity of the magnetic field results in a high concentration of drug being released in that region of the Petri dish, and localized cell death is confirmed by cellular viability assay (Calcein AM).