Search

Chip-to-chip and world-to-chip fluidic interconnections are paramount to enable the passage of liquids between component chips and to/from microfluidic systems. Unfortunately, most interconnect designs add additional physical constraints to chips with each additional interconnect leading to over-constrained microfluidic systems. The competing constraints provided by multiple interconnects induce strain in the chips, creating indeterminate dead volumes and misalignment between chips that comprise the microfluidic system. A novel, gasketless superhydrophobic fluidic interconnect (GSFI) that uses capillary forces to form a liquid bridge suspended between concentric through-holes and acting as a fluid passage was investigated. The GSFI decouples the alignment between component chips from the interconnect function and the attachment of the meniscus of the liquid bridge to the edges of the holes produces negligible dead volume. This passive seal was created by patterning parallel superhydrophobic surfaces (water contact angle ≥ 150°) around concentric microfluidic ports separated by a gap. The relative position of the two polymer chips was determined by passive kinematic constraints, three spherical ball bearings seated in v-grooves. A leakage pressure model derived from the Young–Laplace equation was used to estimate the leakage pressure at failure for the liquid bridge. Injection-molded, Cyclic Olefin Copolymer (COC) chip assemblies with assembly gaps from 3 to 240 µm were used to experimentally validate the model. The maximum leakage pressure measured for the GSFI was 21.4 kPa (3.1 psig), which corresponded to a measured mean assembly gap of 3 µm, and decreased to 0.5 kPa (0.073 psig) at a mean assembly gap of 240 µm. The effect of radial misalignment on the efficacy of the gasketless seals was tested and no significant effect was observed. This may be a function of how the liquid bridges are formed during the priming of the chip, but additional research is required to test that hypothesis.

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.

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]

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.

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

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 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 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

Low-cost microfluidic platforms have the potential to change accepted practices in many fields, including biology and medicine, in the near future. Micro-assembly of molded polymer microfluidic devices is one approach to cost-effective mass production of modular, microfluidic instruments. Polymer, passive alignment structures were used to precisely assemble molded polymer components to prevent infinitesimal motions and minimize the misalignment between assembled components and devices. The motion and constraint of the assemblies were analyzed using screw theory to identify combinations of passive alignment structures that would provide exact constraint of all degrees of freedom of the two mating parts without over-constraint. One option identified by kinematic analysis was a set of three v-groove and hemisphere-tipped pin joints, which are well known from precision engineering and suitable for microfabrication. To validate the passive alignment scheme, brass mold inserts containing alignment structures were micro-milled and used to hot emboss components in polycarbonate (PC). Dimensional and location variations of prototype alignment structures were measured to quantify the difference between the as-designed and actual dimensions and the locations of the alignment structures. The dimensional variation was 0.2–3% less than the designed dimensions and the location variation was 0.7% less. The alignment accuracy of an assembly was characterized by measuring the mismatch and vertical variation between molded alignment standards embossed on each pair of mating plates. With molded, polymer alignment structures the mean mismatch and mean vertical variation were as low as 13 ± 3 µm in the lateral plane along the x- and y-axes and −6 ± 15 µm with respect to the nominal value of 107 µm. This micro-assembly technology is applicable to the integration of all microsystems including the interconnection of microfluidic devices, the assembly of hybrid microsystems and the parallel assembly of microdevices.