Separate Chips Research Articles

Analytical and graphical modelling of the cutting scheme when generating with a pinion cutter

The teeth generation in the case of the cylindrical gears with involute profile is frequently realized with tools of pinion cutter type, on specialized slotting machine tools. In general, during gear teeth machining, several teeth of the tool are concomitantly in contact with the worked part, each one detaching a separate chip. The process is characterized by important unevenness of these chips cumulated area, depending on the relative position between the pinion cutter and the worked part. This transforms into cutting force and cutting torque unevenness and negatively influences both machine tool operating and tool life. The paper addresses the problem of smoothing the detached chips cumulated area at the consecutive strokes of the tool, along the rolling motion between it and the worked part, in order to obtain a main cutting torque as uniform as possible. In this purpose, the analytical modelling of the tool/worked part contact is realized at first, in the cases of generating both exterior and interior gears with involute straight teeth. Then, because the analytical solution is very laborious, a modelling algorithm is developed in one of the most performant graphical environments, which is CATIA. By implementing the graphical solution, the variation of detached chips cumulated area can be determined and the required variation law of the rolling feed, leading to process smoothing, can also be found. A numerical approached case study, concerning the teeth machining for an exterior gear is also presented.

Application of Microfluidic Chips in Separation and Analysis of Extracellular Vesicles in Liquid Biopsy for Cancer.

Extracellular vesicles (EVs) are becoming a promising biomarker in liquid biopsy of cancer. Separation EV from cell culture medium or biofluids with high purity and quality remains a technique challenge. EV manipulation techniques based on microfluidics have been developed in the last decade. Microfluidic-based EV separation techniques developed so far can be classified into two categories: surface biomarker-dependent and size-dependent approaches. Microfluidic techniques allow the integration of EV separation and analysis on a single chip. Integrated EV separation and on-chip analysis have shown great potential in cancer diagnosis and monitoring treatment of responses. In this review, we discuss the development of microfluidic chips for EV separation and analysis. We also detail the clinical application of these microfluidic chips in the liquid biopsy of various cancers.

Design and Characterization of a Micro-Fabricated Graphene-Based MEMS Microphone

We fabricate a microelectromechanical systems (MEMS) microphone that incorporates a graphene-based membrane that vibrates in response to acoustic forcing. We employ a novel fabrication process, where a graphene/poly(methyl methacrylate) (PMMA) bilayer membrane is transferred over a cavity on a separate chip before being affixed to the surface of another chip containing an electrode, resulting in the fabrication of a moveable capacitor with a membrane-to-electrode gap of 8 $\mu \text{m}$ . The gap, which is less than half the size of other reported graphene membrane-based audio transducers, allows for the device to operate with the low-DC bias voltages of about 1 V and, when integrated with a custom-designed readout circuit, demonstrates a sensitivity to sound pressure between 0.1 and 10 mV/Pa across the range 100 Hz–20 kHz. As well as a sensitivity that is comparable with the previous work, the flat frequency response is stable when the sound pressure is varied between 70 and 80 dBSPL, with the sensitivity value not varying by more than 0.2 mV/Pa.

Simple non-galvanic flip-chip integration method for hybrid quantum systems

A challenge faced by experimenters exploring hybrid quantum systems is how to integrate and interconnect different materials and different substrates in a quantum-coherent fashion. Here, we present a simple and inexpensive flip-chip bonding process, suitable for integrating hybrid quantum devices on chips from different substrates. The process only requires equipment and materials used routinely for contact photolithography, and it is possible to undo the bonding and reuse the chips. The technique requires minimal compressive force, so it is compatible with a wide range of different substrates. Unlike indium-based bonding, this process does not establish a galvanic connection between the two chips, but as we show, in some situations this is not necessary. We demonstrate the technique using lithographically patterned quarter-wave coplanar waveguide resonators, fabricated on one chip, and couple these inductively to a transmission line patterned lithographically on a separate chip. The two chips have a vertical interchip gap of about 7 μm, and we can repeatedly achieve lateral alignments of better than 2 μm. We measure electromagnetic resonances with low-power (∼1 photon) internal quality factors Qi around 5 × 105, comparable to single-chip performances, with as-designed coupling quality factors Qc ranging from 2 × 102 to 5 × 105.

Micro- and Nanopillar Chips for Continuous Separation of Extracellular Vesicles.

Micro- and nanopillar chips are widely used to separate and enrich biomolecules, such as DNA, RNA, protein, and cells, as an analytical technique and to provide a confined nanospace for polymer science analyses. Herein, we demonstrated a continuous accurate and precise separation technique for extracellular vesicles (EVs), nanometer-sized vesicles (typically 50-200 nm) currently recognized as novel biomarkers present in biofluids, based on the principle of electroosmotic flow-driven deterministic lateral displacement in micro- and nanopillar array chips. Notably, the easy-to-operate flow control afforded by electroosmotic flow allowed nanoparticles 50-500 nm in size, including EVs, to be precisely separated and enriched in a continuous manner. By observation of the flow behavior of nanoparticles, we found that electroosmotic flow velocity in the nanopillar arrays did not solely depend on counterion mobility on the surface of nanopillar chips, but rather showed a parabolic flow profile. This hydrodynamic pressure-free and easy-to-use separation and enrichment technique, which requires only electrode insertion into the reservoirs and electric field application, may thus serve as a promising technique for future precise and accurate EV analysis, reflecting both size and composition for research and potential clinical diagnostic applications.

Proposed probe chip a potential shortcut for quantum device manufacturing cycle

Alternative method of characterizing semiconductor material properties with a separate probe chip that induces quantum dots could speed optimization of quantum dot spin qubits.

Induced quantum dot probe for material characterization.

We propose a non-destructive means of characterizing a semiconductor wafer via measuring parameters of an induced quantum dot on the material system of interest with a separate probe chip that can also house the measurement circuitry. We show that a single wire can create the dot, determine if an electron is present, and be used to measure critical device parameters. Adding more wires enables more complicated (potentially multi-dot) systems and measurements. As one application for this concept we consider silicon metal-oxide-semiconductor (MOS) and silicon/silicon-germanium quantum dot qubits relevant to quantum computing and show how to measure low-lying excited states (so-called "valley" states). This approach provides an alternative method for characterization of parameters that are critical for various semiconductor-based quantum dot devices without fabricating such devices.

Continuous Cell Characterization and Separation by Microfluidic Alternating Current Dielectrophoresis.

A novel alternating current (ac)-dielectrophoretic (DEP) microfluidic chip for continuous cell characterization and separation is presented in this paper. To generate DEP forces, two electrode-pads are embedded in a set of asymmetric orifices on the opposite sidewalls to produce the nonuniform electric fields. In the vicinity of a small orifice, the cells experience the strongest nonuniform gradient and are drawn toward it by the positive DEP forces, while the cells experiencing a negative DEP force are repelled away and move toward the large orifice. The DEP behaviors of yeast cells in suspending media with different ionic concentrations, i.e., different electrical conductivities, and over a large range of the ac electric field frequency were investigated. Furthermore, the lateral migrations of yeast cells as a function of the ac frequency were measured. The trends of measured lateral migrations of yeast cells are similar to the corresponding Clausius-Mossotti (CM) factors. In addition, by adjusting the frequency and strength of the ac electric field, the continuous separation of live and dead yeast cells as well as the yeast cells with targeted diameter and dielectric property can be easily achieved. This is the first time that the measurement of ac-DEP lateral migration of yeast cells in solutions with different electrical conductivities as a function of the applied frequency in a microfluidic chip was reported. This ac-DEP system provides a method to characterize the crossover frequency of the specific cells and manipulate the targeted cells.

Inkjet 3D printed modular microfluidic chips for on-chip gel electrophoresis

Concept of modular microfluidics combined with fabrication of the modules by 3D printing is an alternative to traditional monolithic form of the chips and microfabrication techniques of microfluidic circuits. Here we propose the modular configuration of the chip for gel electrophoresis of genetic material. The microfludic device is assembled from discrete inkjet 3D printed modules dedicated to a specific function of the chip (i.e. sample introduction/injection, separation and optical detection). Thus, theoretically the separation microchannel could be extended to an almost unlimited length. Moreover, thanks to the modularity of the separation chip, it is possible to transfer a brick with a sample between different configurations of the microfluidic circuits to perform another analysis of the sample. Proof-of-principle tests of the modular configuration and sample transfer were carried out with DNA ladder samples.

Multi-level separation of particles using acoustic radiation force and hydraulic force in a microfluidic chip

Combined with acoustic separation and hydraulic separation technology, a microfluidic chip, which can achieve multi-level particle separation, is proposed in this work. The chip uses the sheath flow on both sides to align the mixed particles in the set area (near the side of the channel) of the separation channel. And then, the mixed particles successively pass through the acoustic surface wave and hydraulic action area, which are generated by modulating interdigital transducers and adjusting the flow ratio, respectively, and finally realize multiple particle separation under the acoustic radiation and hydraulic force. The corresponding separation experiments were carried out using polystyrene (PS) microparticles with diameters of 1 µm, 5 µm, and 10 µm, respectively. Moreover, we explored the influence of the peak-to-peak voltage (Vpp) and flow ratio on the PS microparticles separation effect, and the separation effect is optimal at the flowrate in the main channel is 4 mm/s, Vpp = 25 V, A1 = 0.2, A2 = 0.5. Under these conditions, the separation purity of 1 µm, 5 µm, and 10 µm PS microparticles are 95.60%, 91.67%, 93.75%, respectively, and their separation rates are 96.67%, 89.19%, and 96.77%, respectively. The combined multi-level separation chip has the advantages of simple structure, high separation accuracy, high separation efficiency, and the ability to sort multiple particles, which can be applied to chemical analysis, cell sorting, biomedicine.

THE EFFECTIVENESS OF BIOSERUM INJECTION ON AGARWOOD RESIN (Aquilariamalaccensis) FORMATION WITH SEVERAL INJECTION HOLE DISTANCES

Agarwood has so high value that can trigger an excessive agarwood encroachment in nature; it threatened the agarwood availability. Agarwood cultivation was the right solution to overcome the Agarwood insufficiency. Currently, bioserum has been found to form Agarwood rapidly. It was found by Kusnadi and introduced to the public by BPDASHLWSS (The watershed management and protection forest inquiry). The formation and effectiveness process of bioserum has not been researched yet scientifically. Therefore, this study aimed to determine the success rate of Agarwood formation and the quality of Agarwood with combined injections treatments on tree branches of Aquilariamalaccensis. This research used a complete randomized design with 3 treatments. Each treatment consisted of several vertical injection hole spaces: 5 cm, 10 cm, and 15 cm. The horizontal space for these three treatments was the same, 5 cm. The result showed that the best vertical range of injection was 10 cm. Therefore, each injection hole would produce separate agarwood chips. A 10-cm vertical range injection also made the rest wood between the injection holes not too wide. This Agarwood was classified into kamedangan class with the average weight of 2 g/chips.

Combining 3D sidewall electrodes and contraction/expansion microstructures in microchip promotes isolation of cancer cells from red blood cells

Cell sorting from heterogeneous organisms and tissues composed of multi-type cells is of great importance in biological and clinical applications. As promising cell sorting methods, dielectrophoresis (DEP) and hydrodynamics are attracting much attention in recent years. In this paper, we report a novel strategy by coupling DEP unit (3D sidewall electrodes) and hydrodynamic unit (microchannels with contraction/expansion structures) together in one microfluidic chip. Depending on the relative positions of 3D sidewall electrodes and contraction/expansion structure, three microchips (full-coupling, semi-coupling and non-coupling) are developed and their cell sorting performance are compared by isolating lung cancer cells (PC-9 cells) from red blood cells (RBCs). Both finite element simulation and practical cell sorting prove that high cell sorting efficiency (recovery of PC-9 cells: 90.21%, recovery of RBCs: 94.35%) can be achieved in full-coupling microchip, mainly owing to the synergistic effects between DEP sorting and hydrodynamic sorting. i.e., the positive DEP force generated by 3D sidewall electrodes can simultaneously act as an additional shear gradient lift force and thus trigger secondary flow even at low flow velocity. Live/dead cell staining, hemolysis ratio, fluorescence images and CCK-8 assay prove that RBCs and PC-9 cells show no significance difference in cell viability before and after cell sorting. The proposed coupling platform for cell sorting brings on a new pathway to construct integrated microfluidic chips for effective cell sorting and separation.

Size- and deformability-based isolation of circulating tumor cells with microfluidic chips and their applications in clinical studies

Circulating tumor cells (CTCs) are shed from the primary lesion, entering the blood circulation, and potentially establishing metastasis at distant sites. CTCs play a vital role in cancer metastasis and treatment efficacy evaluation. Separation of CTCs and subsequent characterization has significances in monitoring and diagnosing of cancer. However, isolation of CTCs is technically challenging due to the rareness in patient blood. In the present review, we reviewed recent progress in the design and clinical advance of size and deformability-based CTCs separation chips. We focused on the principle and clinical indicators, such as capture efficiency, throughput, and viability, of devices. Finally, insights in future research and applications are discussed.

Prismatic Deflection of Live Tumor Cells and Cell Clusters.

The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable noninvasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells-properties closely linked to their clinical behavior-demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into 10 discrete streams. Using this approach, we achieve exceptional purity (5.7 log white blood cell depletion) of isolated cells. We test the differential profiling function of the integrated device using prostate cancer blood samples from a mouse xenograft model. Using integrated graphene Hall sensors, we demonstrate concurrent automated profiling of single cells and CTC clusters that belong to distinct subpopulations based on protein surface expression.

Combating Data Leakage Trojans in Commercial and ASIC Applications With Time-Division Multiplexing and Random Encoding

Globalization of microchip fabrication opens the possibility for an attacker to insert hardware Trojans into a chip during the manufacturing process. While most defensive methods focus on detection or prevention, a recent method, called Randomized Encoding of Combinational Logic for Resistance to Data Leakage (RECORD), uses data randomization to prevent hardware Trojans from leaking meaningful information even when the entire design is known to the attacker. Both RECORD and its sequential variant require significant area and power overhead. In this paper, a Time-Division Multiplexed version of the RECORD design process is proposed which reduces area overhead by 63% and power by 56%. This time-division multiplexing (TDM) concept is further refined to allow commercial off the shelf (COTS) products and IP cores to be safely operated from a separate chip. These new methods tradeoff latency ( $5.3\times $ for TDM and $3.9\times $ for COTS) and energy use to accomplish area and power savings and achieve greater security than the original RECORD process.

Nodemcu-based Low-cost Smart Home Node Design

This design proposes a low-cost node solution based on the Wi-Fi wireless sensor network. It aims to solve the problem of the popularity of smart homes due to high costs in real life and is suitable for applications in the smart home field. This solution saves cost, uses SOC solution, and has few peripheral circuits. Nodemcu is used to collect sensor data directly, which saves a separate main control chip, thereby further reducing costs. Various hardware interfaces are provided to facilitate the expansion of different types of sensor functions. The hardware of different functional nodes is designed, and the data is uploaded to a back-end server. Based on the software processing, the data between different nodes is aggregated and uploaded to the cloud platform for display to achieve remote access and control.

Dielectrophoretic separation of microalgae cells in ballast water in a microfluidic chip.

The composition of the ship's ballast water is complex and contains a large number of microalgae cells, bacteria, microplastics, and other microparticles. To increase the accuracy and efficiency of detection of the microalgae cells in ballast water, a new microfluidic chip for continuous separation of microalgae cells based on alternating current dielectrophoresis was proposed. In this microfluidic chip, one piece of 3-dimensional electrode is embedded on one side and eight discrete electrodes are arranged on the other side of the microchannel. An insulated triangular structure between electrodes is designed for increasing the inhomogeneity of the electric field distribution and enhancing the dielectrophoresis (DEP) force. A sheath flow is designed to focus the microparticles near the electrode, so as to increase the suffered DEP force and improve separation efficiency. To demonstrate the performance of the microfluidic separation chip, we developed two species of microalgae cells (Platymonas and Closterium) and a kind of microplastics to be used as test samples. Analyses of the related parameters and separation experiments by our designed microfluidic chip were then conducted. The results show that the presented method can separate the microalgae cells from the mixture efficiently, and this is the first time to separate two or more species of microalgae cells in a microfluidic chip by using negative and positive DEP force simultaneously, and moreover it has some advantages including simple operation, high efficiency, low cost, and small size and has great potential in on-site pretreatment of ballast water.

Carbon Iso-Dielectric Separation (CIDS) on Centrifugal Microfluidic Platforms

Centrifugal microfluidic platforms employ pseudo forces controlled by a spindle motor to automate bioanalytical assays on a single fluidic disc with no need for several syringe pumps [1]. Recently, we employed a portable cutter-plotter to fabricate microfluidic discs with active valves at point of need [2]. To address a healthcare issue of global interest, we developed a microfluidic disc to automate a sTREM-1 immunoassay for the detection of sepsis at late stages of the disease. To enable sepsis detection and monitoring at early stages, recently a gold iso-dielectric separation (GIDS) chip is develop that separates activated and non-activated leukocytes from blood serum [3]. However, the GIDS chip requires several syringe pumps and an off-chip manual step for sample preparation i.e., blood serum separation. As an alternative to GIDS, in this study we have developed 3D carbon IDS (CIDS) chips to reduce the cost of device fabrication. To prevent the need for the syringe pumps and external piping networks, we have integrated the CIDS on a microfluidic disc to automate the whole bioanalytical process from sample preparation to characterization of thousands of particles and cells. The main objective of developing the integrated microfluidic platform is the separation of activated and non-activated leukocytes for automated early sepsis detection at point of care (POC). However, as an early proof of the practicality of CIDS-on-disc, in this study we employed the hybrid centrifugal microfluidic system for separating various sizes of polystyrene microbeads as well as different bacteria. [1] M.M. Aeinehvand, F. Ibrahim, S.W. Harun, A. Kazemzadeh, H.A. Rothan, R. Yusof, M. Madou, Reversible thermo-pneumatic valves on centrifugal microfluidic platforms, Lab Chip. 15 (2015) 3358–3369. doi:10.1039/C5LC00634A. [2] M.M. Aeinehvand, P. Magaña, M.S. Aeinehvand, O. Aguilar, M.J. Madou, S.O. Martinez-Chapa, Ultra-rapid and low-cost fabrication of centrifugal microfluidic platforms with active mechanical valves, RSC Adv. 7 (2017) 55400–55407. doi:10.1039/C7RA11532F. [3] J.L. Prieto, H.-W. Su, H.W. Hou, M.P. Vera, B.D. Levy, R.M. Baron, J. Han, J. Voldman, Monitoring sepsis using electrical cell profiling, Lab Chip. 16 (2016) 4333–4340. doi:10.1039/C6LC00940A.

Deterministic quantum state transfer and remote entanglement using microwave photons.

Sharing information coherently between nodes of a quantum network is fundamental to distributed quantum information processing. In this scheme, the computation is divided into subroutines and performed on several smaller quantum registers that are connected by classical and quantum channels 1 . A direct quantum channel, which connects nodes deterministically rather than probabilistically, achieves larger entanglement rates between nodes and is advantageous for distributed fault-tolerant quantum computation 2 . Here we implement deterministic state-transfer and entanglement protocols between two superconducting qubits fabricated on separate chips. Superconducting circuits 3 constitute a universal quantum node 4 that is capable of sending, receiving, storing and processing quantum information5-8. Our implementation is based on an all-microwave cavity-assisted Raman process 9 , which entangles or transfers the qubit state of a transmon-type artificial atom 10 with a time-symmetric itinerant single photon. We transfer qubit states by absorbing these itinerant photons at the receiving node, with a probability of 98.1 ± 0.1 per cent, achieving a transfer-process fidelity of 80.02 ± 0.07 per cent for a protocol duration of only 180 nanoseconds. We also prepare remote entanglement on demand with a fidelity as high as 78.9 ± 0.1 per cent at a rate of 50 kilohertz. Our results are in excellent agreement with numerical simulations based on a master-equation description of the system. This deterministic protocol has the potential to be used for quantum computing distributed across different nodes of a cryogenic network.

An efficient method for CTCs screening with excellent operability by integrating Parsortix™-like cell separation chip and selective size amplification.

In this article, an attempt for efficient screening of circulating tumor cells (CTCs) with excellent operability on microfluidic chips was reported. A Parsortix™-like cell separation chip was manufactured in our lab. This chip allowed lateral flow of fluid which increased the flow rate of blood. And, an air valve controlled injection pump was manufactured which allowed eight chips working simultaneously. This greatly facilitated the blood treatment process and saved time. As for the mechanism of screening circulating tumor cells, selective size amplification was utilized. By size amplification of cancer cells, both the hardness and the size of CTCs increased which differentiated them from blood cells. And the modification procedure of beads used for size amplification of cancer cells was optimized. Finally, by integrating the commercialized Parsortix™-like cell separation chip and selective size amplification, a practical method for screening circulating tumor cells was established.