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Sodium chloride (NaCl) is the most abundant salt in seawater, which showed the strongest effect in lowering the viscosity of wormlike micellar solutions (WMS) compared to other investigated ionic compounds. In this study, we examined the effect of NaCl addition on the structure of wormlike micelles using the semi-quantitative rheo-structure relations provided by the reaction-reptation model. Prior to addition of NaCl, the structure of wormlike micelles ([CTAB]/[NaSal] = 1 at [CTAB] = 100 mM) in the solution were investigated at different temperatures (25 ℃ ≤ T ≤ 60 ℃). At higher temperatures, shorter relaxation times and lower ratio values for the local minimum of loss modulus G m i n ' ' over the plateau modulus ( G 0 ' ) were observed. Our results showed that while the zero-shear viscosity of WMS decreased by NaCl addition (S = [NaCl]/[CTAB] varied from 0 to 9), its first critical shear rate and shear stress plateau were observed at their higher values. In addition, while the relaxation time of WMS decreased by adding NaCl, values of G m i n ' ' / G 0 ' did not change accordingly. These results indicate that branch points were formed upon the addition of NaCl and led to the shorter relaxation time and lower zero-shear viscosity.

An improved, laser-induced fluorescence-based micro-optical biosensor was designed and fabricated, with cyclic olefin copolymer (COC) optical waveguides, a poly(methyl methacrylate) (PMMA) fluidic substrate with an array of microlenses, and a COC coupling prism integrated with the waveguide substrate or cover plate. The double-sided hot embossed fluidic substrate had sampling zone microchannels on the bottom and microlenses on the top. Dissolved COC injected into polydimethylsiloxane (PDMS) lost molds embedded the waveguides in the PMMA cover plate and formed the integrated coupling prism. The embedded COC waveguide was flycut down to $50~\mu \text{m}$ . The cover plate and shallow, 1:20 aspect ratio, microchannels were thermal fusion bonded using a pressure-assisted boiling point control system, without sagging. The large COC prism coupled better to the waveguide. The highest intensity evanescent excitation of the waveguide was obtained near the critical angle. The maximum signal-to-noise ratio (SNR) was 119 and the lowest detection limit was 7.34 $\times 10^{\mathbf {-20}}$ mol at a SNR of 2 for a $100~\mu \text{m}$ wide by $50~\mu \text{m}$ deep waveguide. The microlenses highly focused the fluorescent radiation in the sampling zone. The microfabricated waveguide enables rapid, low-cost detection of fluorescent samples with high SNR, a low detection limit, and high sampling efficiency. [2020-0067]

A prominent field of study in biosensor development is the study of electric properties which provide valuable insight into the fluids contents. In this research, a non-enzymatic glucose sensor is fabricated, characterised, and employed. The developed device determines the effects of electrode surface area on sensing efficacy, the effects of glucose concentration on impedimetric response, and a real-time measurement of glucose concentration. Deviations throughout the entire glucose range are detected as an inverse of the impedance in the cell due to the inverse relationship of glucose concentration and charge transfer resistance. The continuous monitoring of glucose is demonstrated by a rapid device response over two iterations of glucose concentration in ascending order: 50 μM, 400 μM, and 3.2 mM. At a sustained frequency of 10 kHz, the result shows a stable impedimetric response of 1038, 752, and 688 kΩ, respectively. The validity of the device as a continuous glucose monitoring method is carried out by repeating the cycle and observing the response.

Among various growth processes, hydrothermal synthesis has been widely employed to produce ZnO nanowires because of its simplicity and cost effectiveness. However, the successful hydrothermal synthesis of ZnO nanowires on multi-layered polymer structures has been limited due to growth inhibitors in the polymer. For example, alpha-hydroxy ketone resolved in a UV-curable polyurethane acrylate (PUA) resin forms carboxyl groups (COOH) consisting of hydroxyl groups (OH) on the -position of a carbonyl group (CO) during the UV-curing process. The carboxyl groups suppress the nucleation and growth of ZnO nanowires. In this paper, multi-layered polymer structures were fabricated by liquid transfer imprint lithography (LTIL), and the enriched carboxyl groups on the UV-cured PUA structures were pre-treated with hexamethylenetetramine (HMTA) solution to reduce the inhibitive influence of the carboxyl groups. The HMTA pre-treatment enabled ZnO nanowires to grow hydrothermally on multi-layered PUA structures despite the initial presence of carboxyl groups. Display Omitted Multi-layered polymer structures were fabricated using a polyurethane acrylate by liquid transfer imprint lithography.UV-cured PUA structures have carboxyl groups that suppress the nucleation and growth of ZnO nanowires.Carboxyl groups were pretreated in aqueous hexamethylenetetramine (HMTA) solution prior to ZnO seed layer coating.ZnO nanowires were grown on the multi-layered polymer structures by hydrothermal synthesis.

A multi-scale fluidic motherboard, which can be used in a universal molecular processing system (uMPS) integrated with task-specific processing modules, was designed and fabricated in thermoplastics. The motherboard consists of a coverplate and a substrate. The coverplate included fluidic interconnects and thermal grooves on the top side, and the corresponding interconnects on the bottom side. The substrate was comprised of cell lysis microchannels, micromixers, and flow-connecting microchannels on the top side, and reservoirs for sample inputs and waste output, thermal grooves, and valve seats for flow control on the bottom side. The coverplates and substrates were fabricated with double-sided hot embossing of polycarbonate (PC) using four micromilled brass molds, two for the coverplate and another two for the substrate. Evaluation of the relative front-to-backside alignment for the double-sided hot embossing yielded an accuracy of 25 μm ± 14 μm (average ± standard deviation) for the coverplates and 30 μm ± 20 μm for the substrates. Thermal fusion bonding (TFB) of the coverplate and substrate was done using a spring plunger bonding setup with a range of temperatures and pressures. The motherboard bonded at 154 °C and 12.0 psi for 2 hours in a convection oven produced complete bonding with a little deformation of the valve seats. The complete motherboard will be integrated with the task-specific processing modules in the uMPS for investigating circulating markers from whole blood for precision molecular diagnosis of disease at low cost and with high fidelity.

Demand has increased for the double-sided moulding of microfluidic devices for a series of biochemical analyses. Accurate alignment of mould inserts is a critical aspect to transfer doubled-sided patterns on the top and bottom surfaces of a moulded part. A method of mould alignment was studied for double-sided hot embossing of polymer microfluidic devices. An alignment method was designed using kinematic constraints, and a set of three locating pins. To validate the alignment method, two brass mould inserts with fluidic reservoirs were used for the double-sided moulding of prototype microfluidic devices. The kinematic constraints were used to align the mould inserts with each other on the hot embossing machine. The misalignment of double-sided features on the moulded parts was measured using a measuring microscope. The X- and Y-magnitudes of the mismatches ranged from −28 to 118 µm along the X-axis of the moulded parts. The X- and Y-magnitudes of the mismatches along the Y-axis of the moulded parts varied from −38 to 141 µm. The results of the experiments showed that the mould alignment using kinematic constraints is applicable to the fabrication of double-sided patterns for microfluidic devices.

Hot embossing is one of the most popular fabrication methods to replicate polymer microdevices in the field of micro-fluidics and micro-optics. Numerical models for hot embossing were constructed to analyze the advance of flow front of the molten polymer using commercial software, DEFORM-2D. A hemisphere tipped post, used as an alignment structure in the assembly of micro devices, was modeled to demonstrate the flow behavior of the molten polymer in mold filling. Hot embossing experiments were performed to validate the feasibility of the numerical models. Most of the simulations showed agreement with experiments. The mold filling was estimated with the heights of the embossed posts in the analysis. No significant mold filling with the molten polymer was observed below the glass transition temperature of 105 °C. The mold cavity was completely filled with the polymer at the molding temperature of 137.5 °C and 150 °C while the embossing forces were 300, 600, and 900 N.

Injection molding has been widely used in the manufacturing of various polymer products, including housewares, home appliances, and automotive parts. A disposable medical device based on polymeric material at a low cost is another important area for injection molding. The numerical analysis was performed to predict the potential problem, often occurring during the manufacturing process of the medical device. Computer-aided engineering model was developed using industry-standard molding software, MOLDFLOW®. The flow pattern of the molten polymer was investigated in the replication of butterfly shaped Catheter Support for various catheterization. The flow pattern and temperature distribution of the molded part were investigated through a series of analysis. The results of analysis with original design predicted non-uniform polymer flow with a poor weld line, unbalanced cavity filling, and uneven temperature distribution of the part. An appropriate gate location to achieve uniform flow pattern for mold filling was determined on the base of the predicted results and experience, considering the performance of the product and limitation of the production.

An increasing interest in low-cost polymer micro-fabrication techniques demands an increasing necessity for characterizing such techniques. In this research, polymethylmethacrylate (PMMA) and polydimethylsiloxane (PDMS) microprisms were realized by hot embossing and replica molding processes, respectively. In both replication methods, the polymer microprisms were patterned with the same brass master mold. This mold was fabricated via high precision micro-milling, which accommodates a wide range of achievable sidewall angles and a large workable surface area relative to lithographic fabrication technologies. The pattern designed for replication contained a microprism array of 20 parallel, equal length prisms, grouped into four sets of distinct prism geometries. The four geometries include three triangular microprisms with varying interior angles and one semicircular microprism with a radius of 500 μm. The polymer microprisms replicated by PMMA hot embossing and PDMS replica molding were found to exhibit interior angle reductions relative to the brass master mold dimensions. This paper includes a description and analysis of a surface treatment process by which the RMS surface roughness of the mentioned PMMA microprisms was shown to reduce by 28 % after controlled thermal exposures just above their glass transition temperature.

A computer-aided engineering (CAE) model was developed to analyze the acoustic characteristics of a car cabin. Pro/Engineer Wildfire 4.0 was used to three-dimensionally represent the geometry of the cabin. The CAE, using COMSOL Multiphysics 4.2a, was performed to investigate the distribution of sound pressure fields at natural frequencies. The principle mode indices were (2, 1, 1), (2, 1, 1), (1, 1, 1), and (2, 2, 2), corresponding to the modal coefficients 1, 2, 3, and 4 and the natural frequencies of 179.691, 139.276, 221.620, and 231.386 Hz, respectively. The results of the analysis provided insight into the car cabin design to suppress exterior and interior noise.

The objective of this study is to design and optimize a vertically movable gate field effect transistor (VMGFET) - suitable for low-frequency, high-sensitivity applications - with an emphasis on modal analysis of the suspended gate structure, optimization of mesh density within the employed finite element analysis software, and optimization of the moveable gate dimensions given its relationship with fabrication complexity and the structure’s resonant frequencies. The methods of design, optimization, and analysis were carried out with COMSOL Multiphysics 4.2a under the assumption of no damping with free vibrations. The results indicate optimal dimensions of the suspended gate structure - given constraints on size, resonance, and fabrication complexity - which suggest a beam thickness of 3 µm and a beam width of 15 µm, yielding an upper limit of input force frequencies near 2 kHz.

A novel electrical modelling for a vertically movable gate field effect transistor (VMGFET) for sensing applications is conducted. Presented is the manipulation of threshold voltage and drain current of the VMGFET as a function of the effective charge density and the air gap between the gate and the substrate body. The usage of the VMGFET in depletion mode, while operating in the saturation region, is proposed to prevent an electrostatic attraction between the suspended gate and substrate and to have a linear response of drain current over a varying air gap. The sensitivity of the VMGFET is simulated and shows a constant slope by changing the air gap under the operating conditions, such as working in depletion mode and operating in the saturation region. The sensitivity independence of the gate position is desirable when the VMGFET is applied for physical sensor applications.

Injection molding is one of the most popular manufacturing methods for the cost-effective mass production of the plastic parts. Filling analysis of the molten polymer provides useful information to investigate the process conditions to ensure successful replication. To validate appropriate gate location for a NEEDLE COVER, flow fronts and flow stresses for four different gating options and three different design options are analyzed and compared to the field results. Based on the results, the optimum gate location for the minimum flow stresses and uniform fill patterns appears to be at gate 3. Thus it also provides minimum possibility of part warpage throughout PORT HOUSING and NEEDLE HOUSING. The results of analysis on the increased wall thickness, lower melt temperature, and longer injection time indicated that higher melt temperatures were recommended to achieve successful molding. Injecting the polymer at a longer time (1.2 second) leads to a significant increase in flow stresses throughout the part and the increase of wall thickness achieve successful replication of the parts.

This paper presents the results of an experimental programme to investigate the effects of the concrete mix parameters on the mechanical properties of aerated lightweight aggregate concrete (ALAC). The compressive strength, modulus of elasticity, split tensile strength and Poisson ratio were investigated for 60 different concretes, with densities ranging from 551 to 1948 kg/m3. The two primary mix design variables studied were the volume percentage of air in the matrix (A/M) and the volume percentage of matrix of the total mix (M/T). The test results indicate that both the compressive strength and modulus of elastic are strongly dependent on A/M. However, the effect of M/T depends on the relative strength of the matrix and aggregate. Both compressive strength and modulus increase with matrix content, for the aggregate used and for A/M ratios of approximately 22% and less; otherwise, they decrease. The coefficient of the split tensile strength as a function of density for the aggregate used is lower than that for normal weight concrete. Regression techniques were used to derive models for the properties of the concrete which give adequate predictions.

Composite insulated wall panels using carbon fiber grid in combination with expanded polystyrene (EPS) insulation have been produced for over 5 years. The carbon fiber grid and the EPS act together to provide shear transfer between the wythes of the composite panel. A design procedure has been developed, based on testing at Washington University and North Carolina State University. The approach discussed here is to ensure that the flexural strength, the cracking moment, and the deflection are all within acceptable limits. This paper first discusses the testing that has been performed to develop the material properties used in the design procedure. Then methods for computing the flexural strength, the cracking moment and the deflection are also presented. Deflections are not often an issue and cracking moments can be easily controlled by the amount of prestress. Therefore, the most important concern is providing adequate shear transfer. The design procedures discussed here were later verified by full scale testing at North Carolina State University.

Demolding in thermal imprint lithography is a process to overcome chemical and mechanical interactions of all levels between stamp and substrate formed by the process history, stamp geometries, and materials used, accounting for most of imprint failure. Undesired deformation in resist may occur depending on the stress generated in the resist with respect to the yield stress. In thermal imprint lithography, temperature is one of the most important parameters not only for the flow of resist during the molding process, but also for the demolding because the thermal stress, the friction and adhesion forces, and the mechanical strength of resist are all dependent on temperature even at below the glass transition temperature of the resist. In this paper, we have developed a method via a numerical simulation of the demolding process to determine an optimal demolding temperature that leads to the least resist deformation. Considering the viscoelasticity of the resist and the temperature dependence of friction coefficients at the resist/stamp interface, an optimal temperature was extracted via normalization of the local Von Mises stress in the resist by its yield stress. For a simple two-dimensional model system with Si stamp and PMMA as a resist layer, the optimal demolding temperature was found to be ∼70°C.

The article aimed to analytically investigate the thermophysical behaviors of a ferrofluid in a vertical rectangle with the variation of intensity of the magnetic field, viscosity of the ferrofluid and boundary conditions. The governing equations of the ferrofluid include the continuity, momentum and energy equations for describing the thermal-fluidic behaviors of the ferrofluid and the Maxwell equation and magnetization equation are also added to consider rotating effect of the nano-sized particles. The flow behavior and heat transfer characteristics of the ferrofluid with the intensity of the magnetic field, viscosities of the ferrofluid and boundary conditions were analyzed through isotherms, velocity profiles and both mean and local Nusselt numbers. As a result, the isotherms of the ferrofluid in the vertical rectangle increased with the increase of the magnetic volume fractions and magnetic field intensities. In addition, the mean Nusselt numbers increased with the increase of magnetite volume fractions at all magnetic field intensities because of the combined effects of both heat conduction by magnetite and the magnetic volume force.

Thermal stress and shrinkage were investigated to analyze pattern defects during the cooling and demolding steps in hot embossing. Hot embossing is one of the most popular fabrication methods that replicate polymer microdevices in fields such as micro-fluidics and micro-optics. Numerical models were developed to study the effect of thermal stress and adhesion force on a molded microstructure during the cooling and demolding steps of micro hot embossing. The alignment microstructure, a hemisphere-tipped post, was located at four radial locations of 5, 10, 15, and 20 mm from the center of the polymer substrate to determine the effect of thermal stress and adhesion forces, relative to pattern location, leading to pattern deformation. Results showed that thermal stress increased as the microstructure was moved further away from the center of the polymer substrate due to an increase in shrinkage velocity. Process parameters could be designed to improve replication fidelity by analyzing the stress distribution of a molded microstructure during cooling and demolding.Copyright © 2014 by ASME

Low-cost modular polymer microfluidic platforms integrating several different functional units may potentially reduce the cost of molecular and environmental analyses, and enable broader applications. Proper function of such systems depends on well-characterized assembly of the instruments. Passive alignment is one approach to obtaining such assemblies. Model modular devices containing passive alignment features, hemispherical pins in v-grooves, and integrated alignment standards for characterizing the accuracy of the assemblies were replicated in polycarbonate using doubled-sided injection molding. The dimensions and locations of the assembly features and alignment standards were measured. The assemblies had mismatches from 16 ± 4 to $20\pm 6~\mu $ m along the x -axis and from 103 ± 7 to $118\pm 11~\mu $ m along the y -axis. The vertical variation from the nominal value of $287~\mu $ m ranged from −10 ± 4 to $34\pm 7~\mu $ m. An assembly tolerance model was used to estimate the accuracy of the assemblies based on the manufacturing variations of the alignment structures. Variation of the alignment structure features were propagated through the assembly using Monte Carlo methods. The estimated distributions matched the measured experimental results well, with differences of 2%–13% due to unmodeled aspects of the variations Accurate assembly of advanced polymer microsystems is feasible and predictable in the design phase. [2014-0125]

A polymer-based, multiplex single molecule detection module (SMD) was developed with a fluidic substrate and a cover plate. The fluidic substrate was fabricated using a single-step, double-sided hot embossing in poly(methyl methacrylate) (PMMA) with sampling zone microchannels on the bottom side and microlenses on the top. Shallow sampling zone microchannels (5 μm deep and 100 μm wide) were made to improve sampling efficiency and microlenses were adopted to collect the fluorescent radiation from the sampling zone microchannels. A cyclic olefin copolymer (COC) embedded waveguide in PMMA along with an integrated coupling prism was fabricated using polydimethylsiloxane (PDMS) stencils and melted COC (40% w/v in toluene) on the cover plate. The COC waveguide with a COC integrated coupling prism will be used for evanescent excitation of fluorescent samples in the sampling zone microchannels. The fluidic substrate was bonded with the cover plate using thermal fusion bonding based on a pressure-assisted boiling point control system. This approach allowed for sealing of shallow microchannels without observable sagging of the cover plate, which was confirmed by leakage testing with fluorescent dyes. The completed SMD module will be tested for characterization of the optical performances such as signal-to-noise ratio and sampling efficiency and it will provide the capability for rapid screening of stroke at low cost.Copyright © 2013 by ASME

A cost effective alignment and positioning system was developed for double-sided hot embossing processes using kinematic principles. Alignment tooling located and transferred the top mold insert location to the proper location for the complementary mold insert and hot embossing was performed. The samples were checked for alignment accuracy and consistency. Adjustments were made and sampling repeated and measured. Results showed the alignment system can improve the locating and positioning of the complementary mold insert in relation to the top in a repeatable and cost effective manner.

Numerical analysis to predict the flow behavior of polymers was conducted using commercial finite element software, DEFORM-2D. An alignment structure, a hemisphere-tipped post with an annular ring, was modeled to demonstrate the flow front of the polymer during molding. The cavity filling process was evaluated by measuring the heights of the molded posts and confirmed and validated by experimental data. Estimated and measured heights showed better replication accuracy with the increase of molding temperature and embossing force. Results exposed complete cavity filling at embossing forces of 600 and 900 N at a molding temperature of 137.5°C. The FEM prediction tool can be used to select the adequate process parameters for a high fidelity replication of polymer microstructures.

Minimizing misalignments during the interconnection of microfluidic modules is extremely critical to develop a fully integrated microfluidic device. Misalignments arising during chip-to-chip or world-to-chip interconnections can be greatly detrimental to efficient functioning of microfluidic devices. To address this problem, we have performed numerical simulations to investigate the effect of misalignments arising in three types of interconnection methods: (i) end-to-end interconnection (ii) channel overlap when chips are stacked on top of each other, and (iii) tube-in-reservoir misalignment occurring due to the offset between the external tubing and the reservoir. For the case of end-to-end interconnection, the effect of misalignment was investigated for 0, 13, 50, 58, and 75% reduction in the available flow area at the location of geometrical misalignment. In the channel overlap interconnection method, various possible misalignment configurations were simulated by maintaining the same amount of misalignment (75% flow area reduction). The effect of misalignment in a tube-in-reservoir interconnection was investigated by positioning the tube at an offset of 164 μm from the reservoir center. All the results were evaluated in terms of the equivalent length of a straight pipe. The effect of Reynolds number (Re) was also taken into account by performing additional simulations of aforementioned cases at Re ranging between 0.075 ≤ Re ≤ 75. Correlations were developed and the results were interpreted in terms of equivalent length (Le ). Equivalent length calculations revealed that the effect of misalignment in tube-in-reservoir interconnection method was the least significant when compared to the other two methods of interconnection.

Minimizing misalignments during the interconnection of microfluidic modules is extremely critical to develop a fully integrated microfluidic device. Misalignments arising during chip-to-chip or world-to-chip interconnections can be greatly detrimental to efficient functioning of microfluidic devices. To address this problem, we have performed numerical simulations to investigate the effect of misalignments arising in three types of interconnection methods: (i) end-to-end interconnection (ii) channel overlap when chips are stacked on top of each other, and (iii) tube-in-reservoir misalignment occurring due to the offset between the external tubing and the reservoir. For the case of end-to-end interconnection, the effect of misalignment was investigated for 0, 13, 50, 58, and 75% reduction in the available flow area at the location of geometrical misalignment. In the channel overlap interconnection method, various possible misalignment configurations were simulated by maintaining the same amount of misalignment (75% flow area reduction). The effect of misalignment in a tube-in-reservoir interconnection was investigated by positioning the tube at an offset of 164 μm from the reservoir center. All the results were evaluated in terms of the equivalent length of a straight pipe. The effect of Reynolds number (Re) was also taken into account by performing additional simulations of aforementioned cases at Re ranging between 0.075 ≤ Re ≤ 75. Correlations were developed and the results were interpreted in terms of equivalent length (Le ). Equivalent length calculations revealed that the effect of misalignment in tube-in-reservoir interconnection method was the least significant when compared to the other two methods of interconnection.

This paper presents a numerical study to investigate the effect of geometrical and material transition on the flow and progression of a sample plug in electrokinetic flows. Three cases were investigated: (a) effect of sudden cross-sectional area change (geometrical transition or mismatch) at the interface, (b) effect of only material transition (i.e. varying ζ-potential), and (c) effect of combined material transition and cross-sectional area change at the interface. The geometric transition was quantified based on the ratio of reduced flow area A2 at the mismatch plane to the original cross-sectional area A1. Multiple simulations were performed for varying degrees of area reduction i.e. 0–75% reduction in the available flow area, and the effect of dispersion on the sample plug was quantified by standard metrics. Simulations showed that a 13% combined material and geometrical transition can be tolerated without significant loss of sample resolution. A 6.54% reduction in the flow rates was found between 0% and 75% combined material and geometrical transition.

The flow behavior of polymers was analyzed using a commercial finite element software, DEFORM-2D, for the replication of microstructures. An alignment structure for microassembly, a hemisphere-tipped post, was modeled to demonstrate the polymer flow in hot embossing. The mold filling with polymer was evaluated by the heights of molded posts. The results of simulation showed better replication fidelity of the post with the increase of the molding temperature and displacement of the mold insert. The complete filling of a mold cavity was achieved at the molding temperatures of 112.5, 125, 137.5, and 150°C when the displacements were 1.5, 2.0 and 2.5 mm. The model can be used to design the process parameters for the reliable replication of microstructures.

Arrays of continuous flow thermal reactors were designed, configured, and fabricated in a 96-device (12 × 8) titer-plate format with overall dimensions of 120 mm × 96 mm, with each reactor confined to a 8 mm × 8 mm footprint. To demonstrate the potential, individual 20-cycle (740 nl) and 25-cycle (990 nl) reactors were used to perform the continuous flow polymerase chain reaction (CFPCR) for amplification of DNA fragments of different lengths. Since thermal isolation of the required temperature zones was essential for optimal biochemical reactions, three finite element models, executed with ANSYS (v. 11.0, Canonsburg, PA), were used to characterize the thermal performance and guide system design: (1) a single device to determine the dimensions of the thermal management structures; (2) a single CFPCR device within an 8 mm × 8 mm area to evaluate the integrity of the thermostatic zones; and (3) a single, straight microchannel representing a single loop of the spiral CFPCR device, accounting for all of the heat transfer modes, to determine whether the PCR cocktail was exposed to the proper temperature cycling. In prior work on larger footprint devices, simple grooves between temperature zones provided sufficient thermal resistance between zones. For the small footprint reactor array, 0.4 mm wide and 1.2 mm high fins were necessary within the groove to cool the PCR cocktail efficiently, with a temperature gradient of 15.8 °C/mm, as it flowed from the denaturation zone to the renaturation zone. With temperature tolerance bands of ±2 °C defined about the nominal temperatures, more than 72.5% of the microchannel length was located within the desired temperature bands. The residence time of the PCR cocktail in each temperature zone decreased and the transition times between zones increased at higher PCR cocktail flow velocities, leading to less time for the amplification reactions. Experiments demonstrated the performance of the CFPCR devices as a function of flow velocity, fragment length, and copy number. A 99 bp DNA fragment was successfully amplified at flow velocities from 1 mm/s to 3 mm/s, requiring from 8.16 min for 20 cycles (24.48 s/cycle) to 2.72 min for 20 cycles (8.16 s/cycle), respectively. Yield compared to the same amplification sequence performed using a bench-top thermal cycler decreased nonlinearly from 73% (at 1 mm/s) to 13% (at 3 mm/s) with shorter residence time at the optimal temperatures for the reactions due to increased flow rate primarily responsible. Six different DNA fragments with lengths between 99 bp and 997 bp were successfully amplified at 1 mm/s. Repeatable, successful amplification of a 99 bp fragment was achieved with a minimum of 8000 copies of the DNA template. This is the first demonstration and characterization of continuous flow thermal reactors within the 8 mm × 8 mm footprint of a 96-well micro-titer-plate and is the smallest continuous flow PCR to date.

A high throughput microfluidic system including a 96 continuous flow (CF) thermal reactors and a multi-zone thermal control system was designed and fabricated. An infrared camera (IR) was used to analyze and verify the uniformity of the temperature distribution. Temperature variations from the nominal values were ±2°C in the denaturation zone and ±1°C in the renaturation and extension zones. Six different DNA fragments, with lengths ranging from 99 bp to 997 bp, were obtained from a λ-DNA template, each with a distinct renaturation temperature. As an initial demonstration of the biochemical performance of the polymerase chain reaction (PCR) reactor arrays, a column device comprised of eight 25-cycle CFPCRs was used to amplify identical PCR cocktails for each DNA fragment simultaneously at a flow velocity of 2 mm/s. All but the 997 bp were successfully amplified. Yields for the 99 bp fragment varied from 15%–36% of the amplicon on block thermal cycler. In a second experiment, a row device composed of six 25-cycle CFPCRs was used to successfully, simultaneously amplify cocktails for all six DNA fragment lengths at a flow velocity of 1 mm/s in parallel. Each device in the row had a distinct renaturation temperature to match the DNA fragment length. The parallel thermal arrays can be used in modular systems including both PCR for amplification and, for example, ligase detection reaction (LDR) for mutation detection.Copyright © 2009 by ASME

Metallic large area mold inserts (LAMIs) are essential for the replication of polymer microfluidic devices. Successful molding of micro- or nanoscale features over large areas is dependent on improving the dimensional control of the mold inserts, particularly those fabricated by electrodeposition using the LIGA or UV-LIGA processes. A systematic approach to controlling the internal stress of the nickel deposits, which was essential for predicting the final flatness of the LAMIs prior to electroplating, was carried out. The internal stress of the nickel deposits from a nickel sulfamate solution was estimated using a bent strip stress measurement method after maintaining electroplating chemicals and conditions and reducing contamination. Over-electroplating of the nickel LAMIs was performed on SU-8 electroplating molds on 150 mm diameter Si wafers. Detailed characterization of the nickel LAMIs to determine the relationship between the overall flatness of the LAMIs and the internal stress identified a suitable process window in terms of the current densities (10–20 mA/cm2) and the internal stress (−8.3 ∼ −3.0 MPa) for the high quality nickel LAMIs with an overall flatness of 100 μm.

Validation of a tolerance analysis for the assembly of modular, polymer microfluidic devices was performed using simulations and experiments. A set of three v-groove and hemisphere-tipped post joints was adopted as a model assembly features. An assembly function with assembly feature dimensions and locations was modeled kinematically. Monte Carlo methods were applied to the assembly function to simulate variation of the assembly. Assembly accuracy was evaluated assuming that the variations of the assembly features were randomly distributed. The estimated mismatches were 118 ± 30 μm and 19 ± 13 μm along the X- and Y-axes, respectively. The estimated vertical gap between the modules at the alignment standards along the X- and Y-axes 312 ± 37 μm and 313 ± 37 μm, compared to the designed value of 287 μm. To validate the tolerance model, two micromilled brass mold inserts containing the assembly features and alignment standards were used to double-sided injection mold polymer parts. The accuracy of the assembly of the modular microdevices was estimated by measuring the mismatch and vertical gaps between alignment standards on each axis. The measured lateral mismatches were 103 ± 6 μm and 16 ± 4 μm along the X- and Y-axes, respectively. The vertical gaps measured for the assemblies were 316 ± 4 μm and 296 ± 9 μm at the X- and Y-axes, compared to the designed distance of 287 μm. Simulation and experimental results were in accordance with each other. The models can be used to predict the assembly tolerance of polymer microfluidic devices and have significant potential for enabling the realization of cost-effective mass production of modular instruments.Copyright © 2008 by ASME

A thermal system used to evaluate a high throughput 96 continuous flow polymerase chain reactor (CFPCR) array was designed, fabricated, and tested. Each polymerase chain reactor (PCR) in the array required three different temperature zones to realize denaturaiton at 90°C–94°C, renaturation at 50°C–70°C, and extension at 72°C; a total of 288 temperature zones were required for the 96 CFPCR array. In an initial configuration, 18 copper strips were used to define the 288 temperature zones. Each copper strip was controlled by a PID feedback control loop. Numerical simulations were used to understand the thermal crosstalk phenomena between the micromilled copper strips, which were tightly packed since the high throughput micro-titer plate format restricted each CFPCR to a square 8 mm on a side. The lowest achievable temperature in each renaturation zone in this complicated thermal environment was also identified. Thermal crosstalk limited the minimum renaturation temperature to 61.1°C. An infrared camera was used to investigate the temperature uniformity over a 0.25 mm thick polycarbonate sheet mounted on the thermal system. The temperature distribution was not uniform due to poor contact between the copper strips and device, warm air accumulated between the packed copper strips, and greater heat transfer around the boundaries of the device. More work is required to overcome these limitations and achieve a more uniform temperature distribution for a multi well CFPCR.Copyright © 2008 by ASME

A 96-well solid-phase reversible immobilization (SPRI) reactor plate was designed to demonstrate functional titer plate-based microfluidic platforms. Nickel, large area mold inserts were fabricated using an SU-8 based, UV-LIGA technique on 150 mm diameter silicon substrates. Prior to UV exposure, the prebaked SU-8 resist was flycut to reduce the total thickness variation to less than 5 mum. Excellent UV lithography results, with highly vertical sidewalls, were obtained in the SU-8 by using an UV filter to remove high absorbance wavelengths below 350 nm. Overplating of nickel in the SU-8 patterns produced high quality, high precision, metal mold inserts, which were used to replicate titer plate-based SPRI reactors using hot embossing of polycarbonate (PC). Optimized molding conditions yielded good feature replication fidelity and feature location integrity over the entire surface area. Thermal fusion bonding of the molded PC chips at 150 degrees C resulted in leak-free sealing, which was verified in leakage tests using a fluorescent dye. The assembled SPRI reactor was used for simple, fast purification of genomic DNA from whole cell lysates of several bacterial species, which was verified by PCR amplification of the purified genomic DNA.

A highly parallel, polymerase chain reaction (PCR) multireactor platform is in high demand to satisfy the high throughput requirements for exploiting the accumulated genetic information from the Human Genome Project. By incorporating continuous flow PCR (CFPCR) devices in a polymer 96-well titer plate format, DNA amplification can be performed with steady-state temperature control and faster reaction speed at lower cost. Prior to the realization of a PCR multi-reactor platform, consisting of a sample delivery chip, a PCR multireactor chip, and a thermal cycler, optimization of the geometry for CFPCR devices in a titer plate-based PCR multi-reactor chip based on manufacturing feasibility is necessary. A prototype PCR multi-reactor chip was designed in a 96-well titer plate format with twelve different CFPCR configurations. High quality metallic, large area mold inserts (LAMIs) were fabricated using an SU-8 based UV-LIGA technique by overplating nickel in SU-8 electroplating templates. Micro molding of polycarbonate (PC) was done using hot embossing, resulting in good replication fidelity over the large surface area. Thermal fusion bonding of the molded PC chips using a custom-made bonding jig yielded acceptable sealing results. The manufacturability investigation throughout the design and the process sequence suggested that the microchannel walls require a minimum width of at least 20 μm and an aspect ratio of 2 for structural rigidity. An optimal CFPCR device for use in a PCR multi-reactor chip can be selected with a series of amplification experiments with the development of a thermal cycler.

A 96-well solid-phase reversible immobilization (SPRI) reactor in a micro molded, photo-activated polycarbonate (PPC) chip was designed, fabricated, and used to purify genomic DNA (gDNA) in a highly parallelized fashion. A SPRI reactor was designed to fit in a 96-well microtiter plate format with compatibility to the existing samples/reagents loading technologies. A high quality, metallic, large area mold insert (LAMI) was fabricated using a SU-8 based UV-LIGA technique. Micro molding of polycarbonate (PC) was done using hot embossing, resulting in good replication fidelity over the large surface area. The 96-well PPC-SPRI reactor, assembled by thermal fusion bonding, showed 100% efficiency for simple and fast purification of gDNA from whole cell lysates of bacterial species. The 96- well PPC-SPRI reactor will open up new avenues for low cost, disposable DNA sample purification in high throughput applications.

In molding, geometric variation of molded parts is inevitable since the parts have a thermal history, including expansion and shrinkage, during the molding process. Shrinkage induces variation between the designed dimensions and locations of features on molded parts while the parts are cooled. Characterization of the variation is necessary to ensure dimensional and location integrity. Hot embossing and injection molding were performed in order to assess variation. Measurements were made using a Measurescope (MM-22, Nikon Corp., Kawasaki, Japan). The measured locations and dimensions were compared to estimates obtained using a simple model based on the linear thermal expansion coefficients (CTE) of the molded materials. The measured and the estimated shrinkage from hot embossing were incorporated in the fabrication of microtiter plate-based polymer microfluidic platforms.Copyright © 2007 by ASME

BioMEMS are compact devices which use microfabrication to miniaturize conventional benchtop instruments. The benefits of using micro devices are the need for less chemical reagents, faster processing, and portability. Realizing a powerful sample-to-answer micro system requires more than just microfabrication technology; thermal management, microfluidic control, and interfacing technology must also be considered. You et al. [1] applied kinematic constraint analysis using screw theory to design the assembly features for passive alignment structures for polymer, modular microfluidic devices. Three pairs of v-groove and hemispherical pin joints were chosen as kinematic pairs for mating two modules. Dimensional variation of the assembly features was one of principal contributions to the mismatch of 28 μm-75 μm between stacked plates in assembly that was reported. This was primarily a result of incomplete mold filling and deformation of the passive alignment structures during the demolding process. Hemisphere-tipped recesses, with additional annular walls as dummy structures, were used to designed to achieve better replication by improving polymer filling and reducing the deformation during demolding. In prototype devices, the posts with the annular dummy structures had a mean height of 922.2 μm – 924.1 μm while the original posts without dummy structures had mean heights of 865.3 μm – 891.2 μm in 10 samples under the same embossing conditions for a design height of 925 μm. Alignment accuracy of better than 10 μm was achieved in the assembly of two plates.Copyright © 2007 by ASME

Highly parallelized biochemical analysis is a significant step toward achieving high throughput processing of patient samples for diagnosis and treatment monitoring. The standard microtiter plate is used to carry out multiple reactions for high throughput screening. By incorporating polymer microfluidic devices at each well in the microtiter plate format, the capability of the format could be significantly enhanced for high throughput processing of large numbers of biochemical samples in a cost-effective manner. Low cost replication of the microtiter plates is done using micro molding techniques, so microfabrication technology for making large area mold inserts (LAMIs) containing microfluidic devices at each well of a microtiter plate format is needed. A large area mold insert (LAMI) in the footprint of the standard microtiter plate was fabricated using an SU-8 based UV-LIGA technique. Excellent lithography results, with vertical sidewalls, were obtained by utilizing flycutting to minimize SU-8 film thickness variation and a UV filter for attenuating high absorbance UV wavelengths. Overplating of nickel in the SU-8 polymeric molds was used to make high quality metallic mold inserts with vertical sidewalls. Micro molding of polycarbonate (PC) was done using hot embossing, resulting in good replication fidelity over the large surface area. Thermal fusion bonding of the molded PC chips yielded good sealing results and the developed polymer microfluidic platforms showed good fluidic uniformity.Copyright © 2006 by ASME

Simulations and experiments to assess the predictability of dimensional and locational tolerances of passive alignment structures on injection molded microfluidic components were performed. A center-gated disk with microscale assembly features, to aid metrology, was reproduced using injection molding. The feature dimensions were 100, 200, 300, and 400 μ. Dimensions of the features were measured using optical profilometery and optical microscopy. Simulations using a commercial package overestimated replication fidelity. Mold surface temperatures and injection speeds significantly affected the replication fidelity as the ratio of surface area to volume increased. The location of better replication fidelity, at each mold surface temperature, moved from the edge of the mold cavity to the injection point as the mold surface temperature increased from 100°C to 150°C. Therefore, process parameters and the design of a mold have to be considered for successful replication of the features.Copyright © 2006 by ASME

For connecting polymeric, modular microfluidic devices, precise, passive alignment structures can prevent infinitesimal motions between the devices and minimize misalignment of the devices. The motion and constraint of passive alignment structures were analyzed for the design of assembly features using screw theory. A combination of three v-groove and sphere joints constrained all degrees of freedom of the two mating plates without over-constraint. To validate the designed passive alignment scheme, hot embossing experiments were conducted using a micromilled brass mold insert, containing alignment features. Prototype alignment structures have dimensional variation. The alignment accuracy of the stacked polymeric plates was estimated by the mismatches between alignment marks of two plates. The mismatches ranged from 28 μm to 70 μm.Copyright © 2006 by ASME