An integrated microfluidic system using mannose-binding lectin for bacteria isolation and biofilm-related gene detection

Molecular diagnosis of biofilm-related genes (BRGs) in common bacteria that cause periprosthetic joint infections may provide crucial information for clinicians. In this study, several BRGs, including ica, fnbA, and fnbB, were rapidly detected (within 1 h) with a new integrated microfluidic system. Mannose-binding lectin (MBL)-coated magnetic beads were used to isolate these bacteria, and on-chip nucleic acid amplification (polymerase chain reaction, PCR) was then performed to detect BRGs. Both eukaryotic and prokaryotic MBLs were able to isolate common bacterial strains, regardless of their antibiotic resistance, and limits of detection were as low as 3 and 9 CFU for methicillin-resistant Staphylococcus aureus and Escherichia coli, respectively, when using a universal 16S rRNA PCR assay for bacterial identification. It is worth noting that the entire process including bacteria isolation by using MBL-coated beads for sample pre-treatment, on-chip PCR, and fluorescent signal detection could be completed on an integrated microfluidic system within 1 h. This is the first time that an integrated microfluidic system capable of detecting BRGs by using MBL as a universal capturing probe was reported. This integrated microfluidic system might therefore prove useful for monitoring profiles of BRGs and give clinicians more clues for their clinical judgments in the near future.     

Developing heatable microfluidic chip to generate gelatin emulsions and microcapsules

The heatable microfluidic chip developed herein successfully integrates a microheater and flow-focusing device to generate uniform-sized gelatin emulsions under various flow rate ratios (sample phase/oil phase, Q _s/Q _o) and driven voltages. The gelatin emulsions can be applied to encapsulate vitamin C for drug release. Our goal is to create the thermal conditions for thermo-sensitive hydrogel materials in the microfluidic chip and generate continuous and uniform emulsions under any external environment. The gelatin emulsion sizes have a coefficient of variation of <5 % and can be precisely controlled by altering the flow rate ratio (Q _s/Q _o) and driven voltage. The gelatin emulsion diameters range from 45 to 120 μm. Moreover, various sizes of these gelatin microcapsules containing vitamin C were used for drug release. The developed microfluidic chip has the advantages of a heatable platform in the fluid device, active control over the emulsion diameter, the generation of uniform-sized emulsions, and simplicity. This new approach for gelatin microcapsules will provide many potential applications in drug delivery and pharmaceuticals.     

Anomalous pulse change in gravity-driven microfluidic oscillator and its application to photodiode switching

Electrofluidic analogy is useful because it provides a method to significantly reduce the reliance of microfluidic chips on dynamic off-chip controllers. Among the functions developed by the analogy, conversion from constant to pulsatile pressure is critical and is yet to be studied. Here, unlike its counterpart electrical oscillator generating square pulses more slowly with decreasing the input voltage, we report that a microfluidic oscillator generates sawtooth pressure pulses more rapidly with decreasing the input pressure (P_I) at 1–2 kPa. Further, with decreasing P_I, the oscillator generates square pulses at P_I > 3.4 kPa, but its operation unexpectedly stops at 2.1 < P_I < 3.4 kPa. We analyze its underlying mechanism with a sophisticated model including a dynamic interaction of the oscillator components and reveal the critical role of the dynamic property of oscillator valves. Additionally, we show electrofluidic switching of a photodiode with the oscillator. The understanding obtained in this study would be essential for developing microfluidic circuits using electrofluidic analogy.     

Deterministic lateral displacement (DLD) in the high Reynolds number regime: high-throughput and dynamic separation characteristics

Recent progress in the development of biosensors has created a demand for high-throughput sample preparation techniques that can be easily integrated into microfluidic or lab-on-a-chip platforms. One mechanism that may satisfy this demand is deterministic lateral displacement (DLD), which uses hydrodynamic forces to separate particles based on size. Numerous medically relevant cellular organisms, such as circulating tumor cells (10–15 µm) and red blood cells (6–8 µm), can be manipulated using microscale DLD devices. In general, these often-viscous samples require some form of dilution or other treatment prior to microfluidic transport, further increasing the need for high-throughput operation to compensate for the increased sample volume. However, high-throughput DLD devices will require a high flow rate, leading to an increase in Reynolds numbers (Re) much higher than those covered by existing studies for microscale (≤?100 µm) DLD devices. This study characterizes the separation performance for microscale DLD devices in the high-Re regime (10?<?Re?<?60) through numerical simulation and experimental validation. As Re increases, streamlines evolve and microvortices emerge in the wake of the pillars, resulting in a particle trajectory shift within the DLD array. This differs from previous DLD works, in that traditional models only account for streamlines that are characteristic of low-Re flow, with no consideration for the transformation of these streamlines with increasing Re. We have established a trend through numerical modeling, which agrees with our experimental findings, to serve as a guideline for microscale DLD performance in the high-Re regime. Finally, this new phenomenon could be exploited to design passive DLD devices with a dynamic separation range, controlled simply by adjusting the device flow rate.     

Operating regimes of a magnetic split-flow thin (SPLITT) fractionation microfluidic device for immunomagnetic separation

Magnetic bead-based immunoassays in the microfluidic format have attracted particular interest as it has several advantages over other microfluidic separation techniques. Magnetic split-flow thin fractionation (SPLITT) is a compact version of microfluidic sorting where a bidispersed or polydispersed suspension of magnetic particle–analyte conjugates can be selectively isolated into co-flowing streams of nearly monodispersed particles. Although the device offers capability of identifying and separating more than one target analytes simultaneously, its performance is sensitive to the slightest variation of the operating condition. Herein, we have numerically investigated the performance of a microscale magnetic SPLITT device. Using a coupled Eulerian–Lagrangian approach, we have evaluated the capture efficiency (CE) and separation index (SI) for each particle type collected at their designated outlet of the SPLITT device and identified the best regimes of operating parameters. While the CE figures are found to be best represented by a group variable Π, the SI values are better represented as function of the product of the group variables γ and β; the SI versus Π plots clearly separate into two basic trends: one for constant β (i.e., varying γ) and the other for constant γ (i.e., varying β). Our study prescribes the desired operating regimes of a microfluidic magnetophoretic SPLITT device in a practical immunomagnetic separation application.     

Error bounds for complementarity problems with tridiagonal nonlinear functions

In this paper we consider the complementarity problem NCP(f) with f(x) = Mx + φ(x), where M ∈ R ^n×n is a real matrix and φ is a so-called tridiagonal (nonlinear) mapping. This problem occurs, for example, if certain classes of free boundary problems are discretized. We compute error bounds for approximations \({\hat x}\) to a solution x* of the discretized problems. The error bounds are improved by an iterative method and can be made arbitrarily small. The ideas are illustrated by numerical experiments.     

Isolation of magnetically tagged cancer cells through an integrated magnetofluidic device

Circulating tumour cells (CTC) in the bloodstream has been implicated in cancer metastasis. Efficient removal of CTC could potentially be an effective therapeutic measure against cancer metastasis. In this study, the hydrodynamic focusing flow in microfluidic channels (R _e  ? 1) was considered together with the magnetophoretic force. The localised magnetic field was achieved through a passivated current-carrying multilayered microstripline, where the generated field gradient was used to attract the magnetic beads to the desired outlet. The experimental results show that the device is capable of isolating purely magnetic beads with an efficiency of 91 % while isolation efficiency of the magnetically tagged HeLa cervical cancer cells from cell suspension yielded an isolation efficiency of 79 %.     

Star reduction among minimal length addition chains

An addition chain for a natural number n is a sequence \({1=a_0 < a_1 < \cdots < a_r=n}\) of numbers such that for each 0 < i ≤ r, a _i  = a _j  + a _k for some 0 ≤ k ≤ j < i. The minimal length of an addition chain for n is denoted by ?(n). If j = i ? 1, then step i is called a star step. We show that there is a minimal length addition chain for n such that the last four steps are stars. Then we conjecture that there is a minimal length addition chain for n such that the last \({\lfloor\frac{\ell(n)}{2}\rfloor}\)-steps are stars. We verify that the conjecture is true for all numbers up to 2¹⁸. An application of the result and the conjecture to generate a minimal length addition chain reduce the average CPU time by 23–29% and 38–58% respectively, and memory storage by 16–18% and 26–45% respectively for m-bit numbers with 14 ≤ m ≤ 22.     

On-chip encapsulation via chaotic mixing

A microfluidic device for production of uniform size capsules with a prescribed membrane thickness is described. It is versatile, novel and suitable for various polymerization reactions. Parameters such as polymerization time and reagent concentrations can be precisely tuned to control the membrane properties. The device features a part which allows to overcome the diffusion barrier by initiating interfacial polymerization via chaotic mixing. It also allows the termination of the reaction and the collection of the resulting capsules. We observe different typical dynamical phenomena occurring in capsules during their flow along the microchannel, namely wrinkling of the membrane, parachute and bullet shapes and bursting of the capsules due to strong hydrodynamical flow. In addition to production, the monitoring of capsule dynamics in flow gave a possibility to estimate the elastic surface modulus \(E_{{\rm S}}\) and the membrane thickness t. We found that \(E_{{\rm S}}\) can be as low as 6 × 10^?3 N m^?1 and that the thickness can be below 100 nm. This microfluidic device is therefore capable of producing uniform size capsule solutions with suitable membrane properties for the controlled release of drugs, and as a model system of red blood cells for microhydrodynamics experiments.     

Low-cost origami fabrication of 3D self-aligned hybrid microfluidic structures

3D microfluidic device fabrication methods are normally quite expensive and tedious. In this paper, we present an easy and cheap alternative wherein thin cyclic olefin polymer (COP) sheets and pressure sensitive adhesive (PSA) were used to fabricate hybrid 3D microfluidic structures, by the Origami technique, which enables the fabrication of microfluidic devices without the need of any alignment tool. The COP and PSA layers were both cut simultaneously using a portable, low-cost plotter allowing for rapid prototyping of a large variety of designs in a single production step. The devices were then manually assembled using the Origami technique by simply combining COP and PSA layers and mild pressure. This fast fabrication method was applied, as proof of concept, to the generation of a micromixer with a 3D-stepped serpentine design made of ten layers in less than 8 min. Moreover, the micromixer was characterized as a function of its pressure failure, achieving pressures of up to 1000 mbar. This fabrication method is readily accessible across a large range of potential end users, such as educational agencies (schools, universities), low-income/developing world research and industry or any laboratory without access to clean room facilities, enabling the fabrication of robust, reproducible microfluidic devices.     

Negation-Limited Complexity of Parity and Inverters

In negation-limited complexity, one considers circuits with a limited number of NOT gates, being motivated by the gap in our understanding of monotone versus general circuit complexity, and hoping to better understand the power of NOT gates. We give improved lower bounds for the size (the number of AND/OR/NOT) of negation-limited circuits computing Parity and for the size of negation-limited inverters. An inverter is a circuit with inputs x ₁,…,x _n and outputs ¬ x ₁,…,¬ x _n . We show that: (a) for n=2 ^r ?1, circuits computing Parity with r?1 NOT gates have size at least 6n?log?₂(n+1)?O(1), and (b) for n=2 ^r ?1, inverters with r NOT gates have size at least 8n?log?₂(n+1)?O(1). We derive our bounds above by considering the minimum size of a circuit with at most r NOT gates that computes Parity for sorted inputs x ₁≥???≥x _n . For an arbitrary r, we completely determine the minimum size. It is 2n?r?2 for odd n and 2n?r?1 for even n for ?log?₂(n+1)??1≤r≤n/2, and it is ?3n/2??1 for r≥n/2. We also determine the minimum size of an inverter for sorted inputs with at most r NOT gates. It is 4n?3r for ?log?₂(n+1)?≤r≤n. In particular, the negation-limited inverter for sorted inputs due to Fischer, which is a core component in all the known constructions of negation-limited inverters, is shown to have the minimum possible size. Our fairly simple lower bound proofs use gate elimination arguments in a somewhat novel way.     

Study on TSV isolation liners for a Via Last approach with the use in 3D-WLP for MEMS

This paper discusses approaches for the isolation of deep high aspect ratio through silicon vias (TSV) with respect to a Via Last approach for micro-electro-mechanical systems (MEMS). Selected TSV samples have depths in the range of 170…270 µm and a diameter of 50 µm. The investigations comprise the deposition of different layer stacks by means of subatmospheric and plasma enhanced chemical vapour deposition (PECVD) of tetraethyl orthosilicate; Si(OC₂H₅)₄ (TEOS). Moreover, an etch-back approach and the selective deposition on SiN were also included in the investigations. With respect to the Via Last approach, the contact opening at the TSV bottom by means of a specific spacer-etching method have been addressed within this paper. Step coverage values of up to 74 % were achieved for the best of those approaches. As an alternative to the SiO₂-isolation liners a polymer coating based on the CVD of Parylene F was investigated, which yields even higher step coverage in the range of 80 % at the lower TSV sidewall for a surface film thickness of about 1000 nm. Leakage current measurements were performed and values below 0.1 nA/cm² at 10 kV/cm were determined for the Parylene F films which represents a promising result for the aspired application to Via Last MEMS-TSV.     

Virtual reality software package for implementing motor learning and rehabilitation experiments

Virtual reality games for rehabilitation are attracting increasing growth. In particular, there is a demand for games that allow therapists to identify an individual’s difficulties and customize the control of variables, such as speed, size, distance, as well as visual and auditory feedback. This study presents and describes a virtual reality software package (Bridge Games) to promote rehabilitation of individuals living with disabilities and highlights preliminary researches of its use for implementing motor learning and rehabilitation. First, the study presents seven games in the software package that can be chosen by the rehabilitation team, considering the patient’s needs. All game characteristics are described including name, function presentation, objective and valuable measurements for rehabilitation. Second, preliminary results illustrate some applications of two games, considering 343 people with various disabilities and health status. Based on the results, in the Coincident Timing game, there was a main effect of movement sensor type (in this instance the most functional device was the keyboard when compared with Kinect and touch screen) on average time reached by sample analyzed, F(2, 225) = 4.42, p < 0.05. Similarly, in the Challenge! game, a main effect was found for movement sensor type. However, in this case, touch screen provided better performance than Kinect and Leap Motion, F(2, 709) = 5.90, p < 0.01. Thus, Bridge Games is a possible software game to quantify motor learning. Moreover, the findings suggest that motor skills might be practiced differently depending on the environmental interface in which the game may be used.     

Role of interface shape on the laminar flow through an array of superhydrophobic pillars

In this study, measurements of the pressure drop and the velocity vector fields through a regular array of superhydrophobic pillars were systematically taken to investigate the role of air–water interface shape on laminar drag reduction. A polydimethylsiloxane microfluidic channel was created with a regular array of apple-core-shaped and circular pillars bridging across the entire channel. Due to the shape and hydrophobicity of the apple-core-shaped pillars, air was trapped on the side of the pillars after filling the microchannel with water. The measurements were taken at a capillary number of Ca = 6.6 × 10^?5. The shape of the air–water interface trapped within the superhydrophobic apple-core-shaped pillars was systematically modified from concave to convex by changing the static pressure within the microchannel. The pressure drop through the microchannel containing the superhydrophobic apple-core-shaped pillars was found to be sensitive to the shape of the air–water interface. For static pressures which resulted in the apple-core-shaped superhydrophobic pillars having a circular cross section, D/D ₀ = 1, a drag reduction of 7% was measured as a result of slip along the air–water interface. At large static pressures, the interface was driven into the apple-core-shaped pillars, resulting in decrease in the effective size of the pillars and an increase in the effective spacing between pillars. When combined with a slip velocity measured to be 10% of the average velocity between the pillars, the result was a pressure drop reduction of 18% compared to the circular pillars at a non-dimensional interface diameter of D/D ₀ = 0.8. At low static pressures, the pressure drop increased significantly as the expanded air–water interface constricted flow through the array of pillars even as large interfacial slip velocity was maintained. At D/D ₀ = 1.1, for example, the pressure drop increased by 17% compared to the circular pillar. This drag increase was the result of an increased form drag due to a decrease in porosity and permeability of the pillar array and a decrease in the skin friction drag due to the presence of the air–water interface. For D/D ₀ = 1.1, the slip velocity was measured to be 45% of the average streamwise velocity between the pillars. When compared to no-slip pillars of similar shape, the drag reduction was found to increase from 6 to 9% with increasing convex curvature of the air–water interface.     

Sensitive analysis of glutathione in bacteria and HaCaT cells by polydopamine/gold nanoparticle-coated microchip electrophoresis via online pre-concentration of field-amplified sample stacking

In this paper, polydopamine/gold nanoparticles (PDA/Au NPs) were used to construct a functional film on a glass microfluidic channel surface in microchip electrophoresis (MCE) for the separation of reduced glutathione (GSH) and oxidized glutathione (GSSH). The formation of the PDA/Au NPs was characterized by scanning electron microscopy, transmission electron microscope, UV–Vis spectra and ATR-FTIR. An online pre-concentration strategy involving field-amplified sample stacking was used to determine the sensitivity of the assay for measuring GSH and GSSH in bacteria (Escherichia coli, Staphylococcus aureus and Salmonella enterica serovar Typhimurium) and HaCaT cells samples by MCE with laser-induced fluorescence detection. The influences of the separation voltage, the concentration of the running buffer and the pH value of running buffer, were carefully investigated. Using this studied method, GSH and GSSH could be simultaneously pre-concentrated and separated within 70 s. The limits of detection of GSH and GSSH were as low as 0.81 and 0.91 nM, respectively (S/N = 3), which corresponded to approximately 180–301-fold improvements in peak height. Moreover, this method was successfully applied to the analysis of bacteria (E. coli, S. aureus and S. typhimurium) and HaCaT cell samples with a satisfactory recovery rate.     

An orthogonal analysis method for decoupling the nozzle geometrical parameters of microthrusters

This paper proposes an orthogonal analysis method for decoupling the multiple nozzle geometrical parameters of microthrusters, thus an reconfigured design can be implemented to generate a proper thrust. In this method, the effects of various nozzle geometrical parameters, including throat width W _t , half convergence angle θ _in , half divergence angle θ _out , exit-to-throat section ratio W _e /W _t and throat radius of the curvature R _t /W _t , on the performance of microthrusters are sorted by range analysis. Analysis results show that throat width seriously affects thrust because range value of 67.53 mN is extremely larger than the range value of other geometry parameters. For average specific impulse (ASI), the range value of exit-to-throat section ratio W _e /W _t and half divergence angle θ _out are 4.82 s and 3.72 s, respectively. Half convergence angle with the range value of 0.39 s and throat radius with 0.32 s have less influence on ASI compared with exit-to-throat section ratio and half divergence angle. When increasing the half convergence angle from 10° to 40° and throat radius of the curvature from 3 to 9, average specific impulse initially decreases and then increases. A MEMS solid propellant thruster (MSPT) with the reconfigured geometrical parameters of nozzle is fabricated to verify the feasibility of the proposed method. The thrust of the microthruster can reach 25 mN. Power is estimated to be 0.84 W. This work provides design guideline to reasonably configure geometry parameters of microthruster.     

Filtration of aerosol particles by cylindrical fibers within a parallel and staggered array

The World Health Organization (WHO) in 2013 reported that more than seven million unexpected losses every year are credited to air contamination. Because of incredible adaptability and expense viability of fibrous filters, they are broadly used for removing particulates from gasses. The influence of appropriate parameters, e.g., the fiber arrangement, solid volume fraction (SVF or α), fluid flow face velocity (mean inlet velocity), and filter thickness (I _x ), on pressure drop and deposition efficiency are researched. Furthermore, to study the effects of variation of the laminar flow regime and fiber’s cross-sectional shape on the deposition of particles, only a single square fiber has been placed in a channel. By means of finite volume method (FVM), the 2-D motion of 100–1000 nm particles was investigated numerically. The Lagrangian method has been employed and the Saffman’s lift, Drag, and Brownian forces have been considered to affect this motion. Contribution of increasing the Reynolds number to filtration performance increased with smaller fine aerosols to a level of 59.72 %. However, for over 500 nm, the Re = 100 has more efficient results up to 26.97 %. Remarkably, the single square fiber in Re = 200 regime performs similarly to the optimum choice of multi-fibrous filters. It was portrayed the parallel circular multi-fibrous filter with a ratio of horizontal-to-vertical distances between fibers, l/h = 1.143; α = 0.687, I _x  = 116.572, and h/d _f  = 1.0 is the most efficient filter’s structure. The increase in the ratio of vertical distances between fibers-to-fiber’s diameter (h/d _f ) and decrease in SVF or α, results in a drastically decrement of the filtration performance of both parallel and staggered structures. The obtained results have been validated with previous research findings.     

Threshold quantum secret sharing based on single qubit

Based on unitary phase shift operation on single qubit in association with Shamir’s (t, n) secret sharing, a (t, n) threshold quantum secret sharing scheme (or (t, n)-QSS) is proposed to share both classical information and quantum states. The scheme uses decoy photons to prevent eavesdropping and employs the secret in Shamir’s scheme as the private value to guarantee the correctness of secret reconstruction. Analyses show it is resistant to typical intercept-and-resend attack, entangle-and-measure attack and participant attacks such as entanglement swapping attack. Moreover, it is easier to realize in physic and more practical in applications when compared with related ones. By the method in our scheme, new (t, n)-QSS schemes can be easily constructed using other classical (t, n) secret sharing.     

Subjective visual vertical in virtual reality (Curator SVV): validation and normative data

Subjective visual vertical (SVV) assesses the ability to perceive verticality, which is a measure of vestibular otolithic function. Vestibular lesions influence this perception of verticality. We developed a method using virtual reality (VR) display and an Android software application named ‘Curator SVV’. The virtual reality SVV (Curator SVV) consisted of ten readily identifiable artworks projected by a Samsung phone S6 which is inserted into a virtual reality headset. In the first study, 20 patients had there SVV assessed with two devices: (1) a commercially available SVV measurement device (VestiTest^®) and (2) a virtual reality SVV using the Curator SVV application. In a second study, 32 healthy subjects had their SVV assessed by the Curator SVV application whilst sitting in a chair. In the first study, there was no significant difference (p = 0.44, paired t test and p = 0.01, test of equivalence) between results obtained by Curator SVV and the commercially available device. In the second study, the average angle measured for healthy subjects was 0.00° ± 0.85°. The normal range (mean ± 2 SD) was ± 2° in standard upright position. We were able to demonstrate that the Curator SVV can be readily employed as an objective, non-invasive and affordable means of assessing otolith function in the clinical context. We validated this novel methodology by finding strong quantitative parity between a standard commercial SVV unit and the VR Curator SVV method. Our very lightweight and mobile device can be employed in clinical contexts including at the bedside and in different head and body positions.     

Pairs of Complementary Unary Languages with “Balanced” Nondeterministic Automata

For each sufficiently large n, there exists a unary regular language L such that both L and its complement L ^c are accepted by unambiguous nondeterministic automata with at most n states, while the smallest deterministic automata for these two languages still require a superpolynomial number of states, at least \(e^{\Omega(\sqrt[3]{n\cdot\ln^{2}n})}\). Actually, L and L ^c are “balanced” not only in the number of states but, moreover, they are accepted by nondeterministic machines sharing the same transition graph, differing only in the distribution of their final states. As a consequence, the gap between the sizes of unary unambiguous self-verifying automata and deterministic automata is also superpolynomial.