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Polydimethylsiloxane (PDMS) is a widely used material in laboratories for fabricating microfluidic devices with a rapid and reproducible prototypingability, owing to its inherent properties (e.g., flexibility, air permeability, and transparency). However, the PDMS channel is easily deformed under pressures applied to generate flows because of its elasticity, which can affect the robustness of experiments. In addition, air permeability of PDMS causes the pervaporation of water, and its porous structure absorbs oil and even small hydrophobic molecules, rendering it inappropriate for chemically demanding or day-long experiments. In this study, we develop a rapid and reproducible fabrication method for polymer-based rigid microfluidic devices, using epoxy resin that can overcome the limitations of PDMS channels, which are structurally and chemically robust. We first optimize a high-resolution fabrication protocol to achieve convenient and repeatable prototyping of polymeric devices via epoxy casting using PDMS soft molds. In addition, we compare the velocity changes in PDMS microchannels by tracking fluorescent particles in various flows (~133 μL/min) to demonstrate the structural robustness of the polymeric device. Furthermore, by comparing the adsorption of fluorescent hydrophobic chemicals and the pervaporation through channel walls, we demonstrate the excellent chemical resistance of the polymeric device and its suitability for day-long experiments. The rigid polymeric device can facilitate lab-on-chip research and enable various applications, such as high-performance liquid chromatography, anaerobic bacterial culture, and polymerase chain reaction, which require chemically or physically demanding experiments. [ABSTRACT FROM AUTHOR]

Nanoparticle separation techniques are of significant importance in nanoscience and nanotechnological applications and different concentration gradients, electric/dielectric forces, flow/pressure fields, and acoustic waves have been intensively investigated. However, precise separation of nanoparticles has many technical challenges in terms of sizes, shapes, and material properties, limiting the separation resolution, capability, applicability, throughput and so on. In this study, we present a microfluidic device for continuous separation of nanoparticles by combining diffusiophoresis (DP) and electrophoresis (EP) to achieve high separation performance. Concentration gradients formed from sodium chloride (NaCl) and potassium acetate (K-acetate) passively drive the diffusiophoretic migration of nanoparticles. Simultaneously, a low electric potential is additionally applied to impose a synergistic effect on nanoparticle migration by size and surface charge, which is called low-electric-potential-assisted DP (LEPDP). Using a LEPDP-based separation device, we demonstrate the separation of nanoparticles having different sizes (diameters of 500, 200, and 50 nm) and under different surface-charge conditions (carboxylated polystyrene, silica, and polylactide). The resulting separation performance exceeded 95%, in terms of size uniformity, which is about two times better than that obtained using DP alone. We also emphasize that the enhancement of separation performance only needs a small voltage (<1 V), thereby demonstrating that our multiphysical approach could be utilized for high-resolution and portable nanoparticle separation on a chip without the side effects associated with high electric fields. Lastly, we ensure that rapid and precise bio/chemical sensing and analysis of various nanosized particles would be envisioned by strategically combining two nonlinear but synergistic migration effects. [ABSTRACT FROM AUTHOR]

Recently, microparticles have been used as nanoporous membranes in microfluidic devices, contributing to various bioassays on a chip. Here, we report a self-assembled particle membrane (SAPM) integrated microfluidic device that concentrates particles into an aimed microchamber array by using evaporation-driven capillary forces, and manipulates the chemical environment of the microchamber array by sequentially introducing different solutions. We demonstrate that the SAPM-integrated microchamber array can concentrate microparticles and microbial cells up to 120-fold for 2 h and 35-fold for 1 h, respectively, resulting in remarkably high concentration factors. Additionally, we demonstrate that the microchamber array has high potential as a chemostat-like bioreactor because it can actively manipulate the initial seeding number of bacterial cells and continuously supply and sequentially switch fresh nutrients to them. As an example of various applications, the chemostat-like bioreactor was used as a microbial biosensor platform that enabled microbial sensor cells to respond more efficiently and rapidly to external stimuli, such as heavy metal ions. This was made possible by almost eliminating the initial lag phase that dramatically shortened the whole assay time. Notably, the SAPM-integrated microchamber array not only facilitates various bioassays on a chip but also provides unprecedented experimental platforms to study microorganisms in a simple and convenient manner. [ABSTRACT FROM AUTHOR]

The integration of nanoporous membranes into microfluidic devices allows a wide range of analytical and biochemical applications such as stable concentration gradient generation, sample pre-concentration, and ion and biomolecule filtration in a controllable manner. However, further applications of nanoporous membranes in microfluidic devices require rapid and controllable fabrication methods of various nanoporous precursor materials; currently, few such methods exist. Here, we describe simple and robust methods that can be used for microfabricating four different precursor materials as leakage-tight membranes in a microfluidic channel network. The methods consist of a common integration process and individual solidification processes such as solvent evaporation, UV-curing, and temperature treatment. We demonstrate that the fabricated membranes can be used for electrokinetic, nanofluidic pre-concentration of bio-samples such as proteins, cells, and microspheres on either the anodic or cathodic side of the membranes. In addition, we not only characterize the physicochemical properties of the membranes such as conductance of membrane-integrated microchannels, relative permselectivity, and pre-concentration ability, but also compare fabrication availability, membrane robustness, surface charge density tunability and biocompatibility with buffer solutions. The methods are versatile for many nanoporous precursor materials and easy to control the location and dimension of the membranes. Hence, the methods developed and the characterized properties of the membranes tested in this work could be widely employed for further applications of nanoporous membranes in microfluidic systems. [ABSTRACT FROM AUTHOR]

Most polymer-replica-based microfluidic devices are mainly fabricated by using standard soft-lithography technology so that multi-level masters (MLMs) require multiple spin-coatings, mask alignments, exposures, developments, and bakings. In this paper, we describe a simple method for fabricating MLMs for planar microfluidic channels with multi-level barriers (MLBs). A single photomask is necessary for standard photolithography technology to create a polydimethylsiloxane grey-scale photomask (PGSP), which adjusts the total amount of UV absorption in a negative-tone photoresist via a wide range of dye concentrations. Since the PGSP in turn adjusts the degree of cross-linking of the photoresist, this method enables the fabrication of MLMs for an MLB-integrated microfluidic device. Since the PGSP-based soft-lithography technology provides a simple but powerful fabrication method for MLBs in a microfluidic device, we believe that the fabrication method can be widely used for micro total analysis systems that benefit from MLBs. We demonstrate an MLB-integrated microfluidic device that can separate microparticles. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes a multiplexed microfluidic immunohistochemistry (IHC)/immunocytochemistry (ICC) platform for quantitative proteomic profiling in breast cancer samples. Proteomic profiling via ICC was examined for four breast cancer cell lines (AU-565, HCC70, MCF-7, and SK-BR-3). The microfluidic device enabled 20 ICC assays on a biological specimen at the same time and a 16-fold decrease in time consumption, and could be used to quantitatively compare the expression level of each biomarker. The immunohistochemical staining from the microfluidic system showed an accurate localization of protein and comparable quality to that of the conventional IHC method. Although AU-565 and SK-BR-3 cell lines were classified by luminal subtype and adenocarcinomas and were derived from the same patient, weak p63 expression was seen only in SK-BR-3. The HCC70 cell line showed a triple-negative (estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype and showed only cytokeratin 5 expression, a representative basal/myoepithelial cell marker. To demonstrate the applicability of the system to clinical samples for proteomic profiling, we were also able to apply this platform to human breast cancer tissue. This result indicates that the microfluidic IHC/ICC platform is useful for accurate histopathological diagnoses using numerous specific biomarkers simultaneously, facilitating the individualization of cancer therapy. [ABSTRACT FROM AUTHOR]

We present a diffusion-driven and long-range concentration gradient generator that uses hydrogel as a porous membrane to prevent convection flows but allow the diffusion of cell signaling molecules for the study of bacteria! chemotaxis in a microfluidic device. Using this device, we characterized the critical concentrations associated with the chemotactic responses of cells that initially created a population band and then migrated in bands in the presence of mu!ticoncentration gradients. In addition, this device can be used to study the preferential chemotaxis of bacterial cells toward different carbon sources: glucose, galactose, and mannose were preferred over arabinose and xylose, in this order. This was possible since the device is able to simultaneously produce longrange concentration gradients of different chemicals as well. The method presented in this study is easy to perfonn and the device is cheap to fabricate, so that we believe that these characteristics not only make this device a very useful tool to study the chemotaxis of various, motile microorganisms but also permit parallel experimentation and reduce the time and effort needed in characterizing bacterial responses to various chemicals. [ABSTRACT FROM AUTHOR]

Self-assembled particle membranes (SAPMs), formed by a self-assembly phenomenon of nanoparticles, lend themselves to the facile transport of various ions and molecules, realising the manipulation of bio-samples. Notably, its simple, cost-effective and high throughput fabrication process enables itself to be a unique tool for replacing conventional fabrication methods. This study comprehensively reviews SAPM, from fabrication methods to recent advances in bioanalysis. We firstly categorized the fabrication methods of SAPM, following their working principle: off-chip and on-chip fabrication. Then, we enumerate the application results based on the purpose and the objects' size for manipulation or analysis: ions, molecules, microbes, viruses, cells and particles. As the last statement, we conclude this review and share the author's perspective views on current limitations and the required efforts for solving them. We hope this review article will provide an appropriate guideline for many researchers, thereby widening the spectrum of applications of SAPMs in the future. • We reviewed self-assembled particle membrane (SAPM)-incorporated multiscale micro-/nanofluidic devices for bioanalysis. • Based on their fabricating principles, we present the fabrication procedures for SAPMs; off-chip and on-chip fabrication. • Next, we summarized applications by the target size, such as ions, biomolecules, micro-/nanoparticles, and cells. • Lastly, we discussed the remaining challenges in the related field and possible applications for further development. [ABSTRACT FROM AUTHOR]