Pre-programmable polymer transformers as on-chip microfluidic vacuum generators

This paper develops novel polymer transformers using thermally actuated shape memory polymer (SMP) materials. This paper applies SMPs with thermally induced shape memory effect to the proposed novel polymer transformers as on-chip microfluidic vacuum generators. In this type of SMPs, the morphology of the materials changes when the temperature of materials reaches its glass transition temperature (T _g). The structure of the polymer transformer can be pre-programmed to define its functions, which the structure is reset to the temporary shape, using shape memory effects. When subjected to heat, the polymer transformer returns to its pre-memory morphology. The morphological change can produce a vacuum generation function in microfluidic channels. Vacuum pressure is generated to suck liquids into the microfluidic chip from fluidic inlets and drive liquids in the microchannel due to the morphological change of the polymer transformer. This study adopts a new smart polymer with high shape memory effects to achieve fluid movement using an on-chip vacuum generation source. Experimental measurements show that the polymer transformer, which uses SMP with a T _g of 40°C, can deform 310 μm (recover to the permanent shape from the temporary shape) within 40 s at 65°C. The polymer transformer with an effective cavity volume of 155 μl achieved negative pressures of −0.98 psi. The maximum negative up to −1.8 psi can be achieved with an effective cavity volume of 268 μl. A maximum flow rate of 24 μl/min was produced in the microfluidic chip with a 180 mm long channel using this technique. The response times of the polymer transformers presented here are within 36 s for driving liquids to the end of the detection chamber. The proposed design has the advantages of compact size, ease of fabrication and integration, ease of actuation, and on-demand negative pressure generation. Thus, this design is suitable for disposable biochips that need two liquid samples control. The polymer transformer presented in this study is applicable to numerous disposable microfluidic biochips.     

Inferring (Biological) Signal Transduction Networks via Transitive Reductions of Directed Graphs

In this paper we consider the p-ary transitive reduction (TR _p ) problem where p>0 is an integer; for p=2 this problem arises in inferring a sparsest possible (biological) signal transduction network consistent with a set of experimental observations with a goal to minimize false positive inferences even if risking false negatives. Special cases of TR _p have been investigated before in different contexts; the best previous results are as follows:

A low temperature ultrasonic bonding method for PMMA microfluidic chips

Bonding is a bottleneck for mass-production of polymer microfluidic devices. A novel ultrasonic bonding method for rapid and deformation-free bonding of polymethyl methacrylate (PMMA) microfluidic chips is presented in this paper. Convex structures, usually named energy director in ultrasonic welding, were designed and fabricated around micro-channels and reservoirs on the substrates. Under low amplitude ultrasonic vibration, localized heating was generated only on the interface between energy director and cover plate, with peak temperature lower than T _g (glass transition temperature) of PMMA. With the increasing of temperature, solution of PMMA in isopropanol (IPA) increases and bonding was realized between the contacting surfaces of energy director and cover plate while no solution occurs on the surfaces of other part as their lower temperature. PMMA microfluidic chips with micro-channels of 80 μm × 80 μm were successfully bonded with high strength and low dimension loss using this method.     

Factors affecting the replication quality of micro metal gears produced by μ-PIM

μ-PIM is a promising technology for micro-manufacture, by which complex structured micro components can be produced economically. In this paper, iron micro gear arrays with different diameters were produced by μ-PIM. The influence of die temperature (T _m), the injection pressure (P _i) and the injection speed (V _i) on the replication quality has been studied. The results showed that the replication quality was mainly affected by the T _m. Micro gears with best shape retention were obtained when T _m was set to be 80°C, P _i for 100 MPa and V _i for 60 cm³/s. The green compacts were debinded and subsequently sintered. Micro gears with good shape retention and 0.0053 wt. % residual carbon were obtained after debinding and sintering process. The micro hardness turned out 8 GPa measured by a nano-mechanical test instrument.     

Rapid quantification of bio-particles based on image visualisation in a dielectrophoretic microfluidic chip

We studied an imaging-based technique for the rapid quantification of bio-particles in a dielectrophoretic (DEP) microfluidic chip. Label-free particles could be successively sorted and trapped in a continuous flow manner under the applied alternating current (AC) conditions. Both 2 and 3 μm polystyrene beads at a concentration of 1.0 × 10⁷ particles ml⁻¹ could be rapidly quantified within 5 min in our DEP system. Capturing efficiencies higher than 95% could be 2 μm polystyrene beads with a linear flow speed, applied voltage and frequency of 0.89 mm s⁻¹, 20 V_p-p and 5 MHz. Yeast cells (Candida glabrata and Candida albicans) could also be captured even at a lower concentration of 2.5 × 10⁵ cells ml⁻¹. Images of aggregative particles taken from the designed trapping area were further processed based on the intensity of relative greyscale followed by correction of the particle numbers. The imaging-based quantification method showed higher agreement than that of the conventional counting chamber method and proved the stability and feasibility of our AC DEP system.     

Sensitivity analysis of the rice model WARM in Europe: Exploring the effects of different locations,climates and methods of analysis on model sensitivity to crop parameters

Sensitivity analysis studies how the variation in model outputs can be due to different sources of variation. This issue is addressed, in this study, as an application of sensitivity analysis techniques to a crop model in the Mediterranean region. In particular, an application of Morris and Sobol' sensitivity analysis methods to the rice model WARM is presented. The output considered is aboveground biomass at maturity, simulated at five rice districts of different countries (France, Greece, Italy, Portugal, and Spain) for years characterized by low, intermediate, and high continentality. The total effect index of Sobol' (that accounts for the total contribution to the output variation due a given parameter) and two Morris indices (mean μ and standard deviation σ of the ratios output changes/parameter variations) were used as sensitivity metrics. Radiation use efficiency (RUE), optimum temperature (T_opt), and leaf area index at emergence (LAI_ini) ranked in most of the combinations site × year as first, second and third most relevant parameters. Exceptions were observed, depending on the sensitivity method (e.g. LAI_ini resulted not relevant by the Morris method), or site-continentality pattern (e.g. with intermediate continentality in Spain, LAI_ini and T_opt were second and third ranked; with low continentality in Portugal, RUE was outranked by T_opt). Low σ values associated with the most relevant parameters indicated limited parameter interactions. The importance of sensitivity analyses by exploring site × climate combinations is discussed as pre-requisite to evaluate either novel crop-modelling approaches or the application of known modelling solutions to conditions not explored previously. The need of developing tools for sensitivity analysis within the modelling environment is also emphasized.     

Fabrication and characterization of a polymethyl methacrylate continuous-flow PCR microfluidic chip using CO2 laser ablation

An improved microfabrication method was used to fabricate a continuous-flow PCR (polymerase chain reaction) microfluidic chip on the PMMA substrate using the low-power CO₂ laser ablation technique. The use of the low-power CO₂ laser and the PMMA material could reduce the cost and the time of the fabrication process, especially at the step of laboratory research because of the high flexibility of the laser fabrication technique and the low cost of PMMA. A CO₂ laser output power of 4.5 W and a laser scanning velocity of 76.2 mm/s were chosen to fabricate the chip in this work. The micromachining quality could satisfy the microfluidic requirement of the PCR mixture within the microchannel. Good temperature distribution and gradient were obtained on the PMMA chip with a home-built integrated heating system. An amplification of DNA template with a 990 base pair fragment of Pseudomonas was successfully performed with this chip to characterize its availability and performance with various flow rates.     

A Better Constant-Factor Approximation for Selected-Internal Steiner Minimum Tree

The selected-internal Steiner minimum tree problem is a generalization of original Steiner minimum tree problem. Given a weighted complete graph G=(V,E) with weight function c, and two subsets R ^′ ⊊ R⊆V with |R−R ^′|≥2, selected-internal Steiner minimum tree problem is to find a minimum subtree T of G interconnecting R such that any leaf of T does not belong to R ^′. In this paper, suppose c is metric, we obtain a (1+ρ)-approximation algorithm for this problem, where ρ is the best-known approximation ratio for the Steiner minimum tree problem.     

Design and robustness analysis of structurally decoupled 3-DoF MEMS gyroscope in the presence of worst-case process tolerances

This paper presents design of a structurally decoupled 3-DoF non-resonant MEMS gyroscope with increased robustness and gain. The proposed design utilizes dynamic amplification in 2-DoF drive mode oscillator to achieve large gain. The device performance is verified through behavioral model simulations considering the fabrication limitations of standard electroplated nickel micromachining process, MetalMUMPs, of 20 μm structural layer thickness. A wide operational bandwidth of 1.74 kHz with dynamically amplified again of 0.2 μm is achieved at low actuation voltages. A design sensitivity and Monte Carlo analysis is carried out to show the robustness of the design, without any feedback control, within the fabrication process tolerances. Moreover to verify the device performance under the application of angular velocity, a rate table characterization is carried out which resulted in sense mass displacement of 30 nm corresponding to the rotation induced Coriolis force at actuation voltage of 20 V_acV_{ac} and 30 V_dcV_{dc} with angular rotation of 50 rad/s. Behavioral model simulations proved to be an cost-effective and time-saving alternative to the traditional iterative fabrications and physical level simulations.     

Influence of geometry on hydrodynamic focusing and long-range fluid behavior in PDMS microfluidic chips

Details of hydrodynamic focusing in a 2D microfluidic channel-junction are investigated experimentally and theoretically, especially the effect on the focusing width of volumetric flow ratio r between main and side channels, as well as angle θ between channels. A non-linear relationship is observed where the focus width decreases rapidly with increasing r and levels off at higher values. For the dependence on θ, results from both experiments and modeling show that an increased focusing effect is obtained as θ approaches 90°. Long-range focusing is explored along a 1 cm long channel and it is observed that in the middle section of the channel, a smaller θ induces less divergence. This effect is of importance for microfluidic systems utilizing hydrodynamic focusing in long, straight channels.     

A scaling model for electrowetting-on-dielectric microfluidic actuators

A hydrodynamic scaling model of droplet actuation in an electrowetting-on-dielectric (EWD) actuator is presented that takes into account the effects of contact angle hysteresis, drag from the filler fluid, drag from the solid walls, and change in the actuation force while a droplet traverses a neighboring electrode. Based on this model, the threshold voltage, V _T, for droplet actuation is estimated as a function of the filler medium of a scaled device. It is shown that scaling models of droplet splitting and liquid dispensing all show a similar scaling dependence on [t/ε_r(d/L)]^1/2, where t is insulator thickness and d/L is the aspect ratio of the device. It is also determined that reliable operation of a EWD actuator is possible as long as the device is operated within the limits of the Lippmann–Young equation. The upper limit on applied voltage, V _sat, corresponds to contact-angle saturation. The minimum 3-electrode splitting voltages as a function of aspect ratio d/L < 1 for an oil medium are less than V _sat. However, for an air medium the minimum voltage for 3-electrode droplet splitting exceeds V _sat for d/L ≥ 0.4. EWD actuators were fabricated to operate with droplets down to 35pl. Reasonable scaling results were achieved.

A numerical hydrodynamic and thermal characterization of an inter-strata liquid cooling solution for 3D ICs

A novel integrated thermal management solution is proposed to alleviate hot spots in a contemporary 3D IC architecture. The solution employs a series of integrated microchannels, interconnected through each stratum by through silicon fluidic vias (TSFVs), and permits the transfer of heat, via a coolant, from hot to cold zones. This microfluidic system is driven by an integrated AC electrokinetic pump embedded in the channel walls. Recent advancements in electrokinetic micropump technology have allowed greater increases in fluid velocity (mm/s) while operating within the voltage constraints of a 3D IC. This paper presents a 2D simulation of an electrokinetic micropump operating at V_pp = 1.5 V in a 40 μm channel and examines its velocity profile for six frequencies in the range 100 ≤ ω ≤ 100 MHz. An optimum frequency of 100 kHz was established within this range and this was further examined with a constant heat flux of 186 W/cm2 imposed on the wall for an inlet fluid temperature of 40°C. Temperature profiles are presented at the channel-silicon interface and compared with theory.     

Editing Graphs into Disjoint Unions of Dense Clusters

In the Π-Cluster Editing problem, one is given an undirected graph G, a density measure Π, and an integer k≥0, and needs to decide whether it is possible to transform G by editing (deleting and inserting) at most k edges into a dense cluster graph. Herein, a dense cluster graph is a graph in which every connected component K=(V _K ,E _K ) satisfies Π. The well-studied Cluster Editing problem is a special case of this problem with Π:=“being a clique”. In this work, we consider three other density measures that generalize cliques: (1) having at most s missing edges (s-defective cliques), (2) having average degree at least |V _K |−s (average-s-plexes), and (3) having average degree at least μ⋅(|V _K |−1) (μ-cliques), where s and μ are a fixed integer and a fixed rational number, respectively. We first show that the Π-Cluster Editing problem is NP-complete for all three density measures. Then, we study the fixed-parameter tractability of the three clustering problems, showing that the first two problems are fixed-parameter tractable with respect to the parameter (s,k) and that the third problem is W[1]-hard with respect to the parameter k for 0<μ<1.     

A Fast Algorithm for the Path 2-Packing Problem

Let G be an undirected graph and $\mathcal{T}=\{T_{1},\ldots,T_{k}\}Let G be an undirected graph and T={T₁,?,T_k}\mathcal{T}=\{T_{1},\ldots,T_{k}\} be a collection of disjoint subsets of nodes. Nodes in T ₁∪⋅⋅⋅∪T _k are called terminals, other nodes are called inner. By a T\mathcal{T} -path we mean a path P such that P connects terminals from distinct sets in T\mathcal{T} and all internal nodes of P are inner. We study the problem of finding a maximum cardinality collection ℘ of T\mathcal{T} -paths such that at most two paths in ℘ pass through any node. Our algorithm is purely combinatorial and has the time complexity O(mn ²), where n and m denote the numbers of nodes and edges in G, respectively.     

Approximation Algorithms for Bounded Degree Phylogenetic Roots

The Degree- Δ Closest Phylogenetic k th Root Problem (ΔCPR _k ) is the problem of finding a (phylogenetic) tree T from a given graph G=(V,E) such that (1) the degree of each internal node in T is at least 3 and at most Δ, (2) the external nodes (i.e. leaves) of T are exactly the elements of V, and (3) the number of disagreements, i.e., |E ⊕{{u,v} : u,v are leaves of T and d _T (u,v)≤k}|, is minimized, where d _T (u,v) denotes the distance between u and v in tree T. This problem arises from theoretical studies in evolutionary biology and generalizes several important combinatorial optimization problems such as the maximum matching problem. Unfortunately, it is known to be NP-hard for all fixed constants Δ,k such that either both Δ≥3 and k≥3, or Δ>3 and k=2. This paper presents a polynomial-time 8-approximation algorithm for Δ CPR ₂ for any fixed Δ>3, a quadratic-time 12-approximation algorithm for 3CPR ₃, and a polynomial-time approximation scheme for the maximization version of Δ CPR _k for any fixed Δ and k.     

On-chip PCR amplification of genomic and viral templates in unprocessed whole blood

Performing medical diagnosis in microfluidic devices could scale down laboratory functions and reduce the cost for accessible healthcare. The ultimate goal of such devices is to receive a sample of blood, perform genetic amplification (polymerase chain reaction—PCR) and subsequently analyse the amplified products. DNA amplification is generally performed with DNA purified from blood, thus requiring on-chip implementation of DNA extraction steps with consequent increases in the complexity and cost of chip fabrication. Here, we demonstrate the use of unprocessed whole blood as a source of template for genomic or viral targets (human platelet antigen 1 (HPA1), fibroblast growth factor receptor 2 (FGFR2) and BK virus (BKV)) amplified by PCR on a three-layer microfluidic chip that uses a flexible membrane for pumping and valving. The method depends upon the use of a modified DNA polymerase (Phusion™). The volume of the whole blood used in microchip PCR chamber is 30 nl containing less than 1 ng of genomic DNA. For BKV on-chip whole blood PCR, about 3000 copies of BKV DNA were present in the chamber. The DNA detection method, laser-induced fluorescence, used in this article so far is not quantitative but rather qualitative providing a yes/no answer. The ability to perform clinical testing using whole blood, thereby eliminating the need for DNA extraction or sample preparation prior to PCR, will facilitate the development of microfluidic devices for inexpensive and faster clinical diagnostics.     

Melting temperature prediction by thermoelastic instability: An ab initio modelling,for periclase (MgO)

Melting temperature (T_M) is a crucial physical property of solids and plays an important role for the characterization of materials, allowing us to understand their behavior at non-ambient conditions. The present investigation aims i) to provide a physically sound basis to the estimation of T_M through a “critical temperature” (T_C), which signals the onset of thermodynamic instability due to a change of the isothermal bulk modulus from positive to negative at a given P_C-V_C-T_C point, such that (∂P/∂V)_VC,TC = -(∂²F/∂V²) _VC,TC = 0; ii) to discuss the case of periclase (MgO), for which accurate melting temperature observations as a function of pressure are available. Using first principles calculations, quasi-harmonic approximation and anharmonic correction, we model the Helmholtz potential, i.e. F(V,T), and determine pressure thereby. A comparison between measured and predicted T_M values as a function of pressure shows achievement of an average discrepancy of ~2.9%, in the range 0–25 GPa and 3000–5000 K.     

Microfluidic inverse phase ELISA via manipulation of magnetic beads

We report a new technique for conducting immuno-diagnostics on a microfluidic platform. Rather than handling fluid reagents against a stationary solid phase, the platform manipulates analyte-coated magnetic beads through stationary plugs of fluid reagents to detect an antigenic analyte. These isolated but accessible plugs are pre-encapsulated in a microchannel by capillary force. We call this platform microfluidic inverse phase enzyme-linked immunosorbent assay (μIPELISA). μIPELISA has distinctive advantages in the family of microfluidic immunoassay. In particular, it avoids pumping and valving fluid reagents during assaying, thus leading to a lab-on-a-chip format that is free of instrumentation for fluid actuation and control. We use μIPELISA to detect digoxigenin-labeled DNA segments amplified from E. coli O157:H7 by polymerase chain reaction (PCR), and compare its detection capability with that of microplate ELISA. For 0.259 ng μl⁻¹ of digoxigenin-labeled amplicon, μIPELISA is as responsive as the microplate ELISA. Also, we simultaneously conduct μIPELISA in two parallel microchannels.     

Minimizing total tardiness on parallel machines with preemptions

The basic scheduling problem we are dealing with in this paper is the following one. A set of jobs has to be scheduled on a set of parallel uniform machines. Each machine can handle at most one job at a time. Each job becomes available for processing at its release date. All jobs have the same execution requirement and arbitrary due dates. Each machine has a known speed. The processing of any job may be interrupted arbitrarily often and resumed later on any machine. The goal is to find a schedule that minimizes the sum of tardiness, i.e., we consider problem Q∣r _j ,p _j =p, pmtn∣∑T _j whose complexity status was open. Recently, Tian et al. (J. Sched. 9:343–364, 2006) proposed a polynomial algorithm for problem 1∣r _j ,p _j =p, pmtn∣∑T _j . We show that both the problem P∣ pmtn∣∑T _j of minimizing total tardiness on a set of parallel machines with allowed preemptions and the problem P∣r _j ,p _j =p, pmtn∣∑T _j of minimizing total tardiness on a set of parallel machines with release dates, equal processing times and allowed preemptions are NP-hard. Moreover, we give a polynomial algorithm for the case of uniform machines without release dates, i.e., for problem Q∣p _j =p, pmtn∣∑T _j .