Fig 2 - uploaded by Daniel S.-W. Park
Content may be subject to copyright.
A custom-designed electroplating setup: ( a ) Overall- view of the setup including the electroplating bath, a temperature controller, and a DC power supply; and ( b ) Schematic top- view of the electroplating bath ( F1 and F2 filters, P pump, H heater, and V1 , V2 , and V3 valves). Photographs of ( c ) an electroplating jig before assembly and after assembly ( inset ); and ( d ) a top-view of the electroplating tank showing the plating jig and the anode basket immersed and held by titanium bars in a conductive nickel sulfamate solution
Source publication
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 to...
Similar publications
In order to solve the problem of infestation of fresh fruit after making them into candied fruit and the quality degradation caused by the infestation, a combined ozone–microwave sterilization method was used to treat four candied fruit molds. Response surface optimization analysis showed that when the ozone infusion time was at 10 min (2.642 kg/mL...
In order to solve the problem of infestation of fresh fruit after making them into candied fruit and the quality degradation caused by the infestation, a combined ozone–microwave sterilization method was used to treat four candied fruit molds. Response surface optimization analysis showed that when the ozone infusion time was at 10 min and with 560...
Significance
Drug discovery generally investigates one target at a time, in sharp contrast to living organisms, which mold ligands and targets by evolution of highly complex molecular interaction networks. We recapitulate this modality of discovery by encoding drug structures in DNA, allowing the entire DNA-encoded library to interact with thousand...
Efficient cancer cell capture has been previously demonstrated on functionalized surfaces with defined nanotopography such as nanoscale texture. However, conventional additive and subtractive methods to achieve nanotexture require access to specialized nanofabrication equipment within a dedicated cleanroom environment. Here, we present a technique...
In the past decade, RNA therapeutics have gone from being a promising concept to one of the most exciting frontiers in healthcare and pharmaceuticals. The field is now entering what many call a renaissance or “RNAissance” which is being fueled by advances in genetic engineering and delivery systems to take on more ambitious development efforts. How...
Citations
... The same method has been successfully practiced attaining low temperature bonding of various PMMA [248], PC [249] and cellulose acetate [250] microfluidic chips. ...
The thesis is discussing about ultrafast laser-matter interaction and micromachining of polymeric lab on a chip devices using femtosecond laser.
Relying on this I have fabricated and validated two different prototypes of polymeric lab on a chip, (1) a device for capturing circulating tumour cell and (2) a device for neuronal cell culturing. As part of the fabrication of the lab on a chip, a new simple and low-cost solvent assisted thermal bonding technology has also been established. Furthermore, in order to avoid a time consuming trial and error process, an accurate statistical Design of Experiment procedure to estimate the influence of the laser repetition rate, pulse energy, scanning speed, and hatch distance on the femtosecond laser micro-milled depth of the microstructures has also been defined.
... All of the molded PMMA components and the 250 µm thick cover plates were cleaned using a cleaning protocol [21] and dried in a convection oven at 85 • C overnight. Thermal fusion bonding of the cover sheets with the multi-port chips, modules, and motherboards was done by clamping the cover sheets and the multi-port chips, modules, and motherboards between two glass plates, using paper clips to apply the bonding pressure, and putting the whole setup in a convection oven at 105 • C for 2 hours. ...
Existing methods for sealing chip-to-chip (or module-to-motherboard) microfluidic interconnects commonly use additional interconnect components (O-rings, gaskets, and tubing), and manual handling expertise for assembly. Novel gasketless superhydrophobic fluidic interconnects (GSFIs) sealed by transparent superhydrophobic surfaces, forming liquid bridges between the fluidic ports for fluidic passages were demonstrated. Two test platforms were designed, fabricated, and evaluated, a multi-port chip system (ten interconnects) and a modules-on-a-motherboard system (four interconnects). System assembly in less than 3 sec was done by embedded magnets and pin-in-V-groove structures. Flow tests with deionized (DI) water, ethanol/water mixture, and plasma confirmed no leakage through the gasketless interconnects up to a maximum flow rate of
$100~\mu \text{L}$
/min for the multi-port chip system. The modules-on-a-motherboard system showed no leakage of water at a flow rate of
$20~\mu \text{L}$
/min and a pressure drop of 3.71 psi. Characterization of the leakage pressure as a function of the surface tension of the sample liquid in the multi-port chip system revealed that lower surface tension of the liquid led to lower static water contact angles on the superhydrophobic-coated substrate and lower leakage pressures. The high-density, rapidly assembled, gasketless interconnect technology will open up new avenues for chip-to-chip fluid transport in complex microfluidic modular systems. [2020-0168]
... However, the recovery efficiency of DNA extracted from whole blood was only 27-40%, indicating that microchip with amino-coated surfaces had powerless absorption force and might attract other negative species [42]. Photactivated polycarbonate surface is another commonly used method [43,44]. Witek et al. described a microfluidic device with UV-modified surface [45]. ...
Cell-free DNA (cfDNA), which promotes precision oncology, has received extensive concern because of its abilities to inform genomic mutations, tumor burden and drug resistance. The absolute quantification of cfDNA concentration has been proved as an independent prognostic biomarker of overall survival. However, the properties of low abundance and high fragmentation hinder the isolation and further analysis of cfDNA. Microfluidic technologies and lab-on-a-chip (LOC) devices provide an opportunity to deal with cfDNA sample at a micrometer scale, which reduces required sample volume and makes rapid isolation possible. Microfluidic platform also allow for high degree of automation and high-throughput screening without liquid transfer, where rapid and precise examination and quantification could be performed at the same time. Microfluidic technologies applied in cfDNA isolation and analysis are limited and remains to be further explored. This paper reviewed the existing and potential applications of microfluidic technologies in collection and enrichment of cfDNA, quantification, mutation detection and sequencing library construction, followed by discussion of future perspectives.
... Their small size and high control over parameters such as temperature, pH, salt solution and flow speed allow those micro-reactors to develop an efficiently biochemical reaction, otherwise impossible in the normal industrial processes. PC during the years was successfully functionalized with proteins [140] and nucleic acids [141]. ...
In vitro, tubular-like structures formation with human umbilical vein endothelial cells (HUVECs) was investigated by combining material chemistry functionalization and three-dimensional geometry development. Polycarbonate (PC) was used as a template for the development of the scaffold. Natural polysaccharide’s film based on alternate layer-by-layer (LbL) deposition of hyaluronic acid (HA) and chitosan (CHI), was first applied to PC surface and characterized in terms of thickness growth both, in dry conditions using ellipsometry, and confocal lascar scanning microscopy (CLSM). This first functionalization results in a complete coating of the PC layer. Further biofunctionalization with one adhesive peptide (RGD) and two angiogenetic peptides (SVV and QK) was investigated, immobilizing those peptides on the carboxylic group of HA previously deposited, using the well-known carbodiimide chemistry. The labeled version of each peptide was used to characterize the peptides’ immobilization and penetration into the polyelectrolytes layers, resulting in a successful grafting with complete penetration through the entire thickness of the LbL. In vitro tests were performed using HUVECs to assess their adhesion efficiency and their metabolic activity on the LbL with and without peptide immobilization, resulting in a preliminary improved activity when peptide-combinations is used. Finally, PC micro-channels (μCh) were first developed and characterized, and the rest of the experiments were performed on μCh of 25μm width, functionalized with (HA/CHI)12.5 architecture (PC-LbL) with RGD and QK peptides (PC-RGD+QK) or with RGD and SVV peptides (PC-RGD+SVV). Our first tubulogenesis experiment surprisingly showed the formation of tubular-like structures already after 2h of incubation using the double-peptides combination but only using PC-RGD+QK the tubes were present also after 3 and 4 hours of culture. The co-culture experiment with human pericytes derived from placenta (hPC-PL) demonstrates how the stabilization of the tubes was improved after 3 and 4 hours also for the PC-RGD+SVV sample. Globally our bio-functional material with PC-RGD+QK and PC-RGD+SVV peptides allow the formation of tubular-like structure in both mono and co-culture experiment.
... Previously, our group reported a microfluidic for the μSPE of gDNA and total RNA using a solid-phase reversible immobilization (SPRI) approach. [26][27][28][29][30][31] In these assays, microfluidic devices fabricated in a plastic containing arrays of pillars were used as the μSPE beds. When activating the polymer surface with UV/O 3 to generate -COOH surface functionalities, nucleic acids were selectively extracted through the appropriate composition of the immobilization buffer (IB). ...
... Due to the pillar size and spacing, a Ni/Co mold master was made using a lithographic process (see ESI † and Fig. S4) for the 24-bed configuration. 27 We evaluated PC and COC as possible plastics for the μSPE chip because of our success in using PC as a substrate for the extraction of gDNA and total RNA using SPRI. [26][27][28] COC was tested because of the high efficiency of creating -COOH groups on its surface. ...
... 27 We evaluated PC and COC as possible plastics for the μSPE chip because of our success in using PC as a substrate for the extraction of gDNA and total RNA using SPRI. [26][27][28] COC was tested because of the high efficiency of creating -COOH groups on its surface. 38,39 While PC or COC can be injection molded using a molding master, PC is cheaper and we found that it was more robust for embossing, especially the 24-bed device. ...
Cell-free DNA (cfDNA) is a liquid biopsy marker that can carry signatures (i.e., mutations) associated with certain pathological conditions. Therefore, the isolation of cfDNA from a variety of clinical samples...
... This is a major advantage in the use of the modular microfluidic architecture for clinical diagnostics, which in many cases require biochemical processing using different steps. Although a system was demonstrated for processing one sample in this study, many samples may be handled in parallel by incorporating arrays of similar reactors, such as the micro-titer plate formatted reactors of Park et al. [56] and Chen et al. [15] using similar assembly technology. ...
A method for the design, construction, and assembly of modular, polymer-based, microfluidic devices using simple micro-assembly technology was demonstrated to build an integrated fluidic system consisting of vertically stacked modules for carrying out multi-step molecular assays. As an example of the utility of the modular system, point mutation detection using the ligase detection reaction (LDR) following amplification by the polymerase chain reaction (PCR) was carried out. Fluid interconnects and standoffs ensured that temperatures in the vertically stacked reactors were within ±0.2 C° at the center of the temperature zones and ±1.1 C° overall. The vertical spacing between modules was confirmed using finite element models (ANSYS, Inc., Canonsburg, PA) to simulate the steady-state temperature distribution for the assembly. Passive alignment structures, including a hemispherical pin-in-hole, a hemispherical pin-in-slot, and a plate-plate lap joint, were developed using screw theory to enable accurate exactly constrained assembly of the microfluidic reactors, cover sheets, and fluid interconnects to facilitate the modular approach. The mean mismatch between the centers of adjacent through holes was 64 ± 7.7 μm, significantly reducing the dead volume necessary to accommodate manufacturing variation. The microfluidic components were easily assembled by hand and the assembly of several different configurations of microfluidic modules for executing the assay was evaluated. Temperatures were measured in the desired range in each reactor. The biochemical performance was comparable to that obtained with benchtop instruments, but took less than 45 min to execute, half the time.
... This device (Fig. 3A) achieved 95% recovery in silico at high throughput (1.5 mL/h) and with a surface area (125 cm 2 ) accommodating 10 11-13 EVs (>10 mL blood plasma) and <40 µL internal volume amenable to downstream EV profiling. We are fabricating metal masters by UV-LiGA (Figs. 1A-B, 3B) [6] to mass produce the new EV-MAP devices. ...
Extracellular vesicles (EVs) are nanovesicles (30-500 nm) secreted by cells that protect protein/RNA biomarkers in blood and are key effectors in cancer. However, discerning biologically active subpopulations of cancer-related EVs has proved difficult due to lagging technological developments for EV purification that supersede the "gold standard" differential ultracentrifugation. Herein, we report technologies for the continuous-flow Microfluidic Affinity Purification of EVs (EV-MAP) and EV release for downstream enumeration and molecular profiling. INTRODUCTION Technologies for EV enrichment lag in maturity compared to other liquid biopsy markers. Differential ultracen-trifugation separates EVs by size/density but requires days to complete. Polymer precipitation, filtration, and flow cytometry offer varying recovery, purity, sample capacity, and procedural difficulties; e.g., polymer precipitation is fast and simple, but RNA and protein contaminants are abundant. Affinity-selection with antibodies (Abs) attached to beads or microfluidic devices enhances specificity by targeting EV-specific, cancer antigens [1]. Microfluidics offers an advantage in that sample enrichment can be mated to online analysis, providing a sample in answer out workflow. Expansion and contraction chambers and herringbone grooves have been employed to enhance the diffusion-limited encounter rate of EVs with surface-bound Abs [1]. The field's first feasibility study, the herringbone microfluidic targeting CD63(+) EVs provides ~20 cm 2 surface area (10 10-12 EVs), 1 mL/h through-put, 20 µL volume, and variable EV recovery (42-94%) with evident non-specific artifacts [1]. To enable enrichment of rare cancer EVs for liquid biopsies of cancer, robust microfluidics capable of efficiently, rapidly, and specifically enriching cancer-associated EVs from large volumes of blood plasma are needed.
... Nickel mold inserts fabricated by optical lithography and electroforming process have been used in the past over brass mold inserts because nickel molds allow for higher resolution of microstructures in the final molded samples [10,11]. For example, minimum features of 10 µm with maximum aspect ratio of 5 were realized in a nickel mold insert, which was used for hot embossing of polycarbonate (PC) for a nucleic acid purification application [10]. ...
... Nickel mold inserts fabricated by optical lithography and electroforming process have been used in the past over brass mold inserts because nickel molds allow for higher resolution of microstructures in the final molded samples [10,11]. For example, minimum features of 10 µm with maximum aspect ratio of 5 were realized in a nickel mold insert, which was used for hot embossing of polycarbonate (PC) for a nucleic acid purification application [10]. Similarly the same minimum features with aspect ratio of 4 were demonstrated in a nickel mold insert, which was utilized for hot embossing of polymerbased, continuous flow thermal reactors in PC [11]. ...
... The gap between the two alignment marks was 10 µm, which can be clearly seen in the UV exposure system during the UV lithography process. Dummy patterns were placed in all 13 layers to make sure continuous electroplating [10]. A set of 13 masks was fabricated at the University of Texas at Dallas using a laser writer with 2.5 µm resolution. ...
Fabrication of 2.5D rock-based micromodels with high resolution features is presented using SU-8 multi-layer lithography and nickel electroforming for nickel molds. Processes associated with SU-8 were carefully optimized by the use of the vacuum contact, the use of UV filter, and controls of UV exposure doses and baking times. The use of SU-8 MicroSpray enabled the easy fabrication of multi-layers of SU-8, while exhibiting some total thickness variations. The thirteen layered SU-8 samples showed reliable patterning results for features at 10 and 25 μm resolutions, and minor pattern distortions of features at the 5 μm resolution. Flycutting method employed in multi-layer lithography of SU-8 yielded accurate total thickness control within ±1.5 μm and excellent pattern formation for all of 5, 10, and 25 μm features. Electroforming of nickel was optimized with electroplating bath composition and electroplating parameters such as current density to realize the high resolution nickel mold. The fabricated nickel molds from flycutting based SU-8 samples revealed the feasibility of manufacturing the minimum features down to 5 μm for thirteen layers without any pattern distortions. The replication-based micromolding method will allow for fabrication of micromodels in a variety of materials such as polymers and ceramics. The high resolution, 2.5D micromodels will be used for investigation of pore-scale fluid transport, which will aid in understanding the complicated fluidic phenomena occurring in the 3D reservoir rock.
Copyright © 2015 by ASME Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
... The disadvantage of thermal-assisted bonding technology is the requirement of high temperature and, sometimes, high external pressure [204][205][206][207][208][209][210][211]. These processing conditions degrade polymers and reduce the alignment accuracy. ...
... The devices were made from thermoplastics and could be molded from metal masters in a single step. [34][35][36][37] This dramatically simplified device production by eliminating the need for loading silica beads into small channels or the formation of monoliths. However, to the best of our knowledge, μSPE has yet to be applied for the analysis of membrane proteins from whole cell lysates. ...
We present a novel microfluidic solid-phase extraction (μSPE) device for the affinity enrichment of biotinylated membrane proteins from whole cell lysates. The device offers features that address challenges currently associated with the extraction and purification of membrane proteins from whole cell lysates, including the ability to release the enriched membrane protein fraction from the extraction surface so that they are available for downstream processing. The extraction bed was fabricated in PMMA using hot embossing and was comprised of 3600 micropillars. Activation of the PMMA micropillars by UV/O3 treatment permitted generation of surface-confined carboxylic acid groups and the covalent attachment of NeutrAvidin onto the μSPE device surfaces, which was used to affinity select biotinylated MCF-7 membrane proteins directly from whole cell lysates. The inclusion of a disulfide linker within the biotin moiety permitted release of the isolated membrane proteins via DTT incubation. Very low levels (∼20 fmol) of membrane proteins could be isolated and recovered with ∼89% efficiency with a bed capacity of 1.7 pmol. Western blotting indicated no traces of cytosolic proteins in the membrane protein fraction as compared to significant contamination using a commercial detergent-based method. We highlight future avenues for enhanced extraction efficiency and increased dynamic range of the μSPE device using computational simulations of different micropillar geometries to guide future device designs.
