Polymer Micro/Nanofabrication and Manufacturing.

Polymer microfabrication/nanofabrication and manufacturing are processes that involve the creation of small-scale structures using various polymeric materials [...].

Acoustofluidics-Assisted Coating of Microparticles.

Microparticles have been applied in many areas, ranging from drug delivery, diagnostics, cosmetics, personal care, and the food industry to chemical and catalytic reactions, sensing, and environmental remediation. Coating further provides additional functionality to the microparticles, such as controlled release, surface modification, bio-fouling resistance, stability, protection, etc. In this study, the conformal coating of microparticles with a positively charged polyelectrolyte (polyallylamine hydrochloride, PAH) by utilizing an acoustofluidic microchip was proposed and demonstrated. The multiple laminar streams, including the PAH solution, were formed inside the microchannel, and, under the traveling surface acoustic wave, the microparticles traversed through the streams, where they were coated with PAH. The results showed that the coating of microparticles can be achieved in a rapid fashion via a microfluidic approach compared to that obtained by the batch method. Moreover, the zeta potentials of the microparticles coated via the microfluidic approach were more uniform. For the unfunctionalized microparticles, the charge reversal occurred after coating, and the zeta potential increased as the width of the microchannel or the concentration of the PAH solution increased. As for the carboxylate-conjugated microparticles, the charge reversal again occurred after coating; however, the magnitudes of the zeta potentials were similar when using the microchannels with different widths or different concentrations of PAH solution.

Fabrication of Polymer Microfluidics: An Overview.

Microfluidic platform technology has presented a new strategy to detect and analyze analytes and biological entities thanks to its reduced dimensions, which results in lower reagent consumption, fast reaction, multiplex, simplified procedure, and high portability. In addition, various forces, such as hydrodynamic force, electrokinetic force, and acoustic force, become available to manipulate particles to be focused and aligned, sorted, trapped, patterned, etc. To fabricate microfluidic chips, silicon was the first to be used as a substrate material because its processing is highly correlated to semiconductor fabrication techniques. Nevertheless, other materials, such as glass, polymers, ceramics, and metals, were also adopted during the emergence of microfluidics. Among numerous applications of microfluidics, where repeated short-time monitoring and one-time usage at an affordable price is required, polymer microfluidics has stood out to fulfill demand by making good use of its variety in material properties and processing techniques. In this paper, the primary fabrication techniques for polymer microfluidics were reviewed and classified into two categories, e.g., mold-based and non-mold-based approaches. For the mold-based approaches, micro-embossing, micro-injection molding, and casting were discussed. As for the non-mold-based approaches, CNC micromachining, laser micromachining, and 3D printing were discussed. This review provides researchers and the general audience with an overview of the fabrication techniques of polymer microfluidic devices, which could serve as a reference when one embarks on studies in this field and deals with polymer microfluidics.

Fabrication of Paper-Based Microfluidics by Spray on Printed Paper.

Since the monumental work conducted by Whitesides et al. in 2007, research and development of paper-based microfluidics has been widely carried out, with its applications ranging from chemical and biological detection and analysis, to environmental monitoring and food-safety inspection. Paper-based microfluidics possesses several competitive advantages over other substrate materials, such as being simple, inexpensive, power-free for fluid transport, lightweight, biodegradable, biocompatible, good for colorimetric tests, flammable for easy disposal of used paper-based diagnostic devices by incineration, and being chemically modifiable. Myriad methods have been demonstrated to fabricate paper-based microfluidics, such as solid wax printing, cutting, photolithography, microembossing, etc. In this study, fabrication of paper-based microfluidics was demonstrated by spray on the printed paper. Different from the normally used filter papers, printing paper, which is much more accessible and cheaper, was utilized as the substrate material. The toner was intended to serve as the mask and the patterned hydrophobic barrier was formed after spray and heating. The processing parameters such as toner coverage on the printing paper, properties of the hydrophobic spray, surface properties of the paper, and curing temperature and time were systematically investigated. It was found that, after repetitive printing four times, the toner was able to prevent the hydrophobic spray (the mixture of PDMS and ethyl acetate) from wicking through the printing paper. The overall processing time for fabrication of paper-based microfluidic chips was less than 10 min and the technique is potentially scalable. Glucose detection was conducted using the microfluidic paper-based analytical devices (µPADs) as fabricated and a linear relationship was obtained between 1 and 10 mM.

Constructing a superhydrophobic surface on polydimethylsiloxane via spin coating and vapor-liquid sol-gel process.

In this study, a superhydrophobic surface on polydimethylsiloxane (PDMS) substrate was constructed via the proposed vapor-liquid sol-gel process in conjunction with spin coating of dodecyltrichlorosilane (DTS). Unlike the conventional sol-gel process where the reaction takes place in the liquid phase, layers of silica (SiO(2)) particles were formed through the reaction between the reactant spin-coated on the PDMS surface and vapor of the acid solution. This led to the SiO(2) particles inlaid on the PDMS surface. Followed by subsequent spin coating of DTS solution, the wrinkle-like structure was formed, and the static contact angle of the water droplet on the surface could reach 162 degrees with 2 degrees sliding angle and less than 5 degrees contact angle hysteresis. The effect of layers of SiO(2) particles, concentrations of DTS solution and surface topography on superhydrophobicity of the surface is discussed.

One-Step Hot Microembossing for Fabrication of Paper-Based Microfluidic Chips in 10 Seconds.

In recent years, microfluidic paper-based analytical devices (µPADs) have been developed because they are simple, inexpensive and power-free for low-cost chemical, biological and environmental detection. Moreover, paper is lightweight; easy to stack, store and transport; biodegradable; biocompatible; good for colorimetric tests; flammable for easy disposal of used paper-based diagnostic devices by incineration; and can be chemically modified. Different methods have been demonstrated to fabricate µPADs such as solid wax printing, craft cutting, photolithography, etc. In this study, one-step hot microembossing was proposed and demonstrated to fabricate µPADs. The processing parameters like embossing temperature, pressure and time were systematically investigated. It was found that, at 55 °C embossing temperature, the embossing pressure ranging from 10 to 14 MPa could be applied and the embossing time was only 5 s. This led to the overall processing time for fabrication of µPADs within 10 s. Glucose detection was conducted using the µPADs as fabricated, and a linear relationship was obtained between 5 and 50 mM.

Applications of microfluidics in microalgae biotechnology: A review.

Microalgae have been one of the important sources for biofuel production owing to their competitive advantages such as no need to tap into the global food supply chain, higher energy density, and absorbing carbon dioxide to mitigate global warming. One of the key factors to ensure successful biofuel production is that it requires not only bioprospecting of the microalgae with high lipid content, high growth rate and tolerance to environmental parameters but also on-site monitoring of the cultivation process and optimization of the culturing conditions. However, as the conventional techniques usually involve in complicated procedures, or are time-consuming or labor intensive, microfluidics technology offers an attractive alternative to resolve these issues. In this review, applications of microfluidics to bioprospecting in microalgae biotechnology were discussed such as cell identification, cell sorting/screening, cell culturing and cell disruption. In addition, utilization of microalgae in micro-sized fuel cells and microfluidic platforms for biosensing was addressed. This review reports the recent studies and offers a look into how microfluidics is exploited to tackle the issues encountered in the microalgae biotechnology.

Membrane filtration: An unconventional route for fabrication of the flexible and dissolvable, polymer microneedle patches.

Utilization of dissolvable, polymer microneedles (MNs) for transdermal drug delivery offers many advantages such as being painless to patients, biocompatibility, biodegradability, and active and controlled drug release. There are many different approaches for fabrication of such MNs; however, most of them still suffer from tedious procedures, stringent fabrication conditions, expensive equipment, or substantially long processing time. In this work, we applied membrane filtration to fabricate dissolvable, polymer MNs. The polydimethylsiloxane mold having pyramidal wells with through holes was constructed and placed on top a filter membrane. The polymer solution was then dispensed on top of the mold, followed by turning on the vacuum for filtration. It was found that, when using 22% polyvinylpyrrolidone (PVP) solution with molecular weight of 360 000 g/mol, the PVP MNs were obtained within 1 h, which is relatively short time compared to the conventional methods like casting in conjunction with vacuum or centrifugation. Moreover, the MNs as fabricated possessed the similar mechanical strength compared to those by conventional methods and were able to penetrate the rat ear skin with a high insertion ratio. The proposed technique provides an attractive alternative to fabricate dissolvable and flexible, polymer MNs with a simple setup and easy procedures.

Black silicon SERS substrate: effect of surface morphology on SERS detection and application of single algal cell analysis.

In this study, we have investigated the effect of the surface morphology of the black silicon substrate on surface enhanced Raman spectroscopy (SERS) and explored its application of single algal cell detection. By adjusting the O2 and SF6 flow rates in the cryogenic plasma etching process, different surface morphologies of the black silicon substrate was produced without performing the lithographic process. It was found the Raman signals were better enhanced as the tip density of the black silicon substrate increased. In addition, as the thickness of the deposited gold layer increased, the SERS effect increased as well, which could be owing to the generation of more hot spots by bridging individual silicon tips through deposition of gold layer. For the black silicon substrate with tip density of 30 tips/µm(2) and covered by 400 nm deposited gold layer, the detection limit of 10 fM R6G solution concentration with uniform SERS effect across the substrate was achieved. Furthermore, detection of individual algal cell (Chlorella vulgaris) was performed at the SERS substrate as fabricated and the Raman signals of carotenoid and lipid were substantially enhanced.

Polydimethyl siloxane wet etching for three dimensional fabrication of microneedle array and high-aspect-ratio micropillars.

Among various transdermal drug delivery (TDD) approaches, utilizing the microneedles (MNs) not only can penetrate the skin but also deliver the drug with reduced tissue damage, reduced pain, and no bleeding. However, the MNs with larger height are required to overcome the skin barrier for effective TDD. Unlike 2D patterning, etching polydimethyl siloxane (PDMS) micropillars for fabrication of 3D microstructures is presented. The PDMS micropillars were first constructed by casting PDMS on the computer numerical control-machined cylindrical microwells, which then went through etching process to obtain the MNs for subsequent fabrication of polymer MNs or high aspect ratio micropillars.

Development of flow through dielectrophoresis microfluidic chips for biofuel production: Sorting and detection of microalgae with different lipid contents.

In this study, a continuous flow dielectrophoresis (DEP) microfluidic chip was fabricated and utilized to sort out the microalgae (C. vulgaris) with different lipid contents. The proposed separation scheme is to allow that the microalgae with different lipid contents experience different negative or no DEP force at the separation electrode pair under the pressure-driven flow. The microalgae that experience stronger negative DEP will be directed to the side channel while those experience less negative or no DEP force will pass through the separation electrode pair to remain in the main channel. It was found that the higher the lipid content inside the microalgae, the higher the crossover frequency. Separation of the microalgae with 13% and 21% lipid contents, and 24% and 30%-35% lipid contents was achieved at the operating frequency 7 MHz, and 10 MHz, respectively. Moreover, separation can be further verified by measurement of the fluorescence intensity of the neutral lipid inside the sorted algal cells.

Electrokinetic trapping and surface enhanced Raman scattering detection of biomolecules using optofluidic device integrated with a microneedles array.

In this study, microneedles which possess sharp tips were utilized to trap and detect the biomolecules. Owing to the large curvature, the tips of the microneedles created a substantially high gradient of electric field under the non-uniform electric field which served as not only the trapping sites but also the substrate for surface enhanced Raman scattering (SERS). Separation of polystyrene microparticles with different sizes and two kinds of biomolecules (Staphylococcus aureus (S. aureus) and the red blood cells (RBCs)) were demonstrated. Moreover, in situ detection of S. aureus was performed immediately after separation was completed. The results showed that, after 15 s of sample collection, the Raman signals of S. aureus were detected and greatly enhanced through SERS effect.

Separation of microalgae with different lipid contents by dielectrophoresis.

In this study, the effect of the solution conductivity on the behavior of microalgal cells (Chlorella) with different lipid contents under a non-uniform electric field was investigated. It was found that, for the algal cells with 11 wt% lipid content, the crossover frequency is between 2 and 10 MHz when the solution conductivity is within 1.4 and 2.95 mS/cm, and increases as the solution conductivity increases. As to the microalgal cells with 45 wt% lipid content, they experienced negative DEP at frequency below 20 MHz when the solution conductivity is within 2.06 and 2.95 mS/cm. However, positive DEP was observed when the solution conductivity becomes 1.4 mS/cm. In a mixture of the algal cells, those with different lipid contents were successfully separated by DEP at solution conductivity of 2.95 mS/cm and frequency of 20 MHz.

Fabrication of long poly(dimethyl siloxane) nanochannels by replicating protein deposit from confined solution evaporation.

A relatively simple, inexpensive and reliable technique was developed to fabricate an array of nanochannels. Moreover, the nanochannels are directly integrated to microchannels as a whole, which facilitates solution loading from the millimeter-scaled loading reservoirs into the nanochannels. It is found that continuous bovine serum albumin (BSA) line structures with triangle-like cross section at nanoscale can be obtained by evaporation of BSA solution with concentration between 0.5 wt. % and 1 wt. % inside the microchannels. The poly(dimethyl siloxane) nanochannels were replicated from these line structures, followed by sealing with the glass slide. The DNA molecules can be stretched inside the nanochannels as fabricated.

Packaging of microfluidic chips via interstitial bonding technique.

In this paper, we describe an interstitial bonding technique for packaging of microfluidic chips. The cover plate is first placed on top of the microfluidic chip, followed by dispensing the UV-curable resin into the resin-loading reservoirs. With the interstitial space between the cover plate and the microfluidic chip connecting to the loading reservoirs, the UV-curable resin wicks through capillary force action and hydrostatic pressure generated by the liquid level in the resin-loading reservoirs. When reaching the microchannels, the UV-curable resin stops flowing into the microchannels due to the force balance between the surface tension and hydrostatic pressure. The assembly is then placed under the UV light, followed by further curing in the thermal oven. It is found that there is no leakage from the bonded microfluidic chips and a good DNA separation result was obtained by using the microfluidic chips as fabricated. This bonding technique is relatively simple and fast, which can be applied to the packaging of microfluidic chips made from hybrid materials with complicated designs as long as the interstitial space connects to the loading reservoirs.

Long-range and superfast trapping of DNA molecules in an ac electrokinetic funnel.

In this work we report a microfluidic platform capable of trapping and concentrating a trace amount of DNA molecules efficiently. Our strategy invokes nonlinear electro-osmotic flow induced by charge polarization under high-frequency ac fields. With the asymmetric quadrupole electrode design, a unique converging flow structure can be created for generating focusing effects on DNA molecules. This focusing in turn transforms into a robust funnel that can collect DNA molecules distantly from the bulk and pack them into a compact cone with the aid of short-range dipole-induced self-attraction and dielectrophoresis. Our results reveal that not only can DNA molecules be concentrated within just a few seconds, but also they can be focused into threads of 1 mm in length, demonstrating the superfast and long-range trapping capability of this funnel. In addition, pico M DNA solutions can be concentrated with several decades of enhancement without any continuous feeding. Alternating concentration and release of DNA molecules is also illustrated, which has potentials in concentrating and transporting biomolecules in a continuous fashion using microdevices.

New valve and bonding designs for microfluidic biochips containing proteins.

Two major concerns in the design and fabrication of microfluidic biochips are protein binding on the channel surface and protein denaturing during device assembly. In this paper, we describe new methods to solve these problems. A "fishbone" microvalve design based on the concept of superhydrophobicity was developed to replace the capillary valve in applications where the chip surface requires protein blocking to prevent nonspecific binding. Our experimental results show that the valve functions well in a CD-like ELISA device. The packaging of biochips containing pre-loaded proteins is also a challenging task since conventional sealing methods often require the use of high temperatures, electric voltages, or organic solvents that are detrimental to the protein activity. Using CO2 gas to enhance the diffusion of polymer molecules near the device surface can result in good bonding at low temperatures and low pressure. This bonding method has little influence on the activity of the pre-loaded proteins after bonding.

Microfluidic enzyme-linked immunosorbent assay technology.

In this chapter, we have presented an overview of microfluidic enzyme-linked immunosorbent assay (ELISA) by first introducing the principle of immunoassay, ELISA, and microfabricated devices, followed by a discussion of microfabrication technology and the characterization of microfluidic components. Significant advances in laboratory technology are contributing to the further understanding of microfluidic function, surface modification and immobilization, which lead to the development of improved biomolecule detection methods and prospective applications. For the future, the exploitation of more robust-manufacturing processes and integrated assay systems in an automatic fashion with much reduced assay time and reagent consumption will allow for the effective detection and quantification of biological agents that are of interest in medical diagnostics, food safety surveillance, and environmental monitoring.

Surface modification for enhancing antibody binding on polymer-based microfluidic device for enzyme-linked immunosorbent assay.

A novel surface treatment method using poly(ethyleneimine) (PEI), an amine-bearing polymer, was developed to enhance antibody binding on the poly(methyl methacrylate) (PMMA) microfluidic immunoassay device. By treating the PMMA surface of the microchannel on the microfluidic device with PEI, 10 times more active antibodies can be bound to the microchannel surface as compared to those without treatment or treated with the small amine-bearing molecule, hexamethylenediamine (HMD). Consequently, PEI surface modification greatly improved the immunoassay performance of the microfluidic device, making it more sensitive and reliable in the detection of IgG. The improvement can be attributed to the spacer effect as well as the functional amine groups provided by the polymeric PEI molecules. Due to the smaller dimensions (140x125 microm) of the microchannel, the time required for antibody diffusion and adsorption onto the microchannel surface was reduced to only several minutes, which was 10 times faster than the similar process carried out in 96-well plates. The microchip also had a wider detection dynamic range, from 5 to 1000 ng/mL, as compared to that of the microtiter plate (from 2 to 100 ng/mL). With the PEI surface modification, PMMA-based microchips can be effectively used for enzyme linked immunosorbent assays (ELISA) with a similar detection limit, but much less reagent consumption and shorter assay time as compared to the conventional 96-well plate.