Determination of inorganic ions using microfluidic devices

The separation and detection of inorganic ions on microfluidic devices has received little attention since the 'lab-on-a-chip' concept has revolutionised the field of electrokinetically driven analysis. This review presents a summary and discussion of the published literature on inorganic analysis using microfluidic devices and includes sections on electromigration separation methods, namely isotachophoresis (ITP), capillary electrophoresis (CE), and hyphenated ITP-CE, together with a brief account of flow injection analysis. The review concludes with the authors' perspective on future directions for inorganic analysis on microfluidic devices.     

Synthesis of monodisperse biodegradable microgels in microfluidic devices

Microgels are promising materials in drug delivery and biomedicine. Although monodisperse microgels would offer considerable advantages, most microgels investigated and used today are polydisperse in size. We report on the fabrication of 10 mum sized monodisperse microgels by emulsifying an aqueous dextran-hydroxyethyl methacrylate (dex-HEMA) phase within an oil phase at the junction of microfluidic channels. Dex-HEMA microgels are biodegradable and are ideally suited for the controlled delivery of proteins.     

On-demand preparation of quantum dot-encoded microparticles using a droplet microfluidic system

Optical barcoding technology based on quantum dot (QD)-encoded microparticles has attracted increasing attention in high-throughput multiplexed biological assays, which is realized by embedding different-sized QDs into polymeric matrixes at precisely controlled ratios. Considering the advantage of droplet-based microfluidics, producing monodisperse particles with precise control over the size, shape and composition, we present a proof-of-concept approach for on-demand preparation of QD-encoded microparticles based on this versatile new strategy. Combining a flow-focusing microchannel with a double T-junction in a microfluidic chip, biocompatible QD-doped microparticles were constructed by shearing sodium alginate solution into microdroplets and on-chip gelating these droplets into a hydrogel matrix to encapsulate CdSe/ZnS QDs. Size-controllable QD-doped hydrogel microparticles were produced under the optimum flow conditions, and their fluorescent properties were investigated. A novel multiplex optical encoding strategy was realized by loading different sized QDs into a single droplet (and thus a hydrogel microparticle) with different concentrations, which was triggered by tuning the flow rates of the sodium alginate solutions entrapped with different-colored QDs. A series of QD-encoded microparticles were controllably, and continuously, produced in a single step with the present approach. Their application in a model immunoassay demonstrated the potential practicability of QD-encoded hydrogel microparticles in multiplexed biomolecular detection. This simple and robust strategy should be further improved and practically used in making barcode microparticles with various polymer matrixes.     

Macro-to-micro interfaces for microfluidic devices

Since the concept of miniaturized total analysis systems (microTAS) was invented, a great number of microfluidic devices have been demonstrated for a variety of applications. However, an important hurdle that still needs to be cleared is the connection of a microfluidic device with the rest of the world, which is often referred to as the macro-to-micro interface, interconnect, or world-to-chip interface. In this review, we will examine the methods used by pioneers in the field and other investigators, review the approaches for capillary electrophoresis-based devices and those using pneumatic pumping, and present additional discussion on interface standardization and choosing and designing interconnects for your applications.     

Fabrication of microfluidic devices using photopatternable hybrid sol-gel coatings

UV-patternable organic-inorganic hybrid sol-gel coating was used to develop microchannel on silicon and glass wafers by photolithography processing. The sol-gel coating was formed with 3-methacryloxypropyltrimethoxysilane (MPTS) as photosensitive component and zirconium propoxide as property modifier. In order to enhance the UV light efficiency during photolithography processing for glass substrates, a thin copper layer with thickness of 100–200 nm was deposited on one side of the glass wafer. The closed microchannels were formed by bonding of two developed surface channels of compensating patterns by wafer bonding technology. The bonding material is the same as the channel body ensuring a uniform surface property for the microchannels. A thin layer of about 2 μm was applied on the developed channels by spin coating. The depth of the surface channels on each wafer is about 10–12 μm, and the height of the closed channels is therefore in the range of 22–24 μm. Different microfluidic devices such as chaotic micromixers and microsplitters were fabricated.     

Fabrication of microfluidic devices using dry film photoresist for microchip capillary electrophoresis

An inexpensive, disposable microfluidic device was fabricated from a dry film photoresist using a combination of photolithographic and hot roll lamination techniques. A microfluidic flow pattern was prefabricated in a dry film photoresist tape using traditional photolithographic methods. This tape became bonded to a poly(methyl methacrylate) (PMMA) sheet with prepouched holes when passed through a hot roll laminator. A copper working electrode and platinum decoupler was readily incorporated within this microchip. The integrated microchip device was then fixed in a laboratory-built Plexiglas holder prior to its use in microchip capillary electrophoresis. The performance of this device with amperometric detection for the separation of dopamine and catechol was examined. The separation was complete within 50 s at an applied potential of 200 V/cm. The relative standard deviations (RSD) of analyte migration times were less than 0.71%, and the theoretical plate numbers for dopamine and catechol were 3.2 x 10(4) and 4.1 x 10(4), respectively, based on a 65 mm separation channel.     

Surface modification for PDMS-based microfluidic devices

This review focuses on advances reported from April 2009 to May 2011 in PDMS surface modifications for the application in microfluidic devices. PDMS surface modification techniques presented here include improved plasma and graft polymer coating, dynamic surfactant treatment, hydrosilylation-based surface modification and surface modification with nanomaterials such as carbon nanotubes and metal nanoparticles. Recent efforts to generate topographical and chemical patterns on PDMS are also discussed. The described surface modifications not only increase PDMS wettability, inhibit or reduce non-specific adsorption of hydrophobic species onto the surfaces in the act, but also result in the display of desired functional groups useful for molecular separations, biomolecular detection via immunoassays, cell culture and emulsion formation.     

Hydrogel-based reconfigurable components for microfluidic devices

In situ liquid-phase photopolymerization (LP(3)) has been applied to the field of microfluidics to create components within integrated systems. As an extension of LP(3) technology, we present reconfigurable components that utilize the swelling of hydrogels. These components can be conveniently used to enhance microfluidic functions and applications. In order to utilize the swelling characteristic of hydrogels to the fullest, we demonstrate strategies to increase the swelling performance temporally and spatially. To this end, two successful applications using the reconfigurable components were tested: (1) active walls to block or divert flow at different steps in the fabrication or assay process, and (2) delivery pistons to move objects to specific locations within the microchannels after device fabrication.     

Unconventional detection methods for microfluidic devices

The direction of modern analytical techniques is to push for lower detection limits, improved selectivity and sensitivity, faster analysis time, higher throughput, and more inexpensive analysis systems with ever-decreasing sample volumes. These very ambitious goals are exacerbated by the need to reduce the overall size of the device and the instrumentation - the quest for functional micrototal analysis systems epitomizes this. Microfluidic devices fabricated in glass, and more recently, in a variety of polymers, brings us a step closer to being able to achieve these stringent goals and to realize the economical fabrication of sophisticated instrumentation. However, this places a significant burden on the detection systems associated with microchip-based analysis systems. There is a need for a universal detector that can efficiently detect sample analytes in real time and with minimal sample manipulation steps, such as lengthy labeling protocols. This review highlights the advances in uncommon or less frequently used detection methods associated with microfluidic devices. As a result, the three most common methods - LIF, electrochemical, and mass spectrometric techniques - are omitted in order to focus on the more esoteric detection methods reported in the literature over the last 2 years.     

Wirelessly powered microfluidic dielectrophoresis devices using printable RF circuits

We report the first microfluidic device integrated with a printed RF circuit so the device can be wirelessly powered by a commercially available RFID reader. For conventional dielectrophoresis devices, electrical wires are needed to connect the electric components on the microchip to external equipment such as power supplies, amplifiers, function generators, etc. Such a procedure is unfamiliar to most clinicians and pathologists who are used to working with a microscope for examination of samples on microscope slides. The wirelessly powered device reported here eliminates the entire need for wire attachments and external instruments so the operators can use the device in essentially the same manner as they do with microscope slides. The integrated circuit can be fabricated on a flexible plastic substrate at very low cost using a roll-to-roll printing method. Electrical power at 13.56 MHz transmitted by a radio-frequency identification (RFID) reader is inductively coupled to the printed RFIC and converted into 10 V DC (direct current) output, which provides sufficient power to drive a microfluidic device to manipulate biological particles such as beads and proteins via the DC dielectrophoresis (DC-DEP) effect. To our best knowledge, this is the first wirelessly powered microfluidic dielectrophoresis device. Although the work is preliminary, the device concept, the architecture, and the core technology are expected to stimulate many efforts in the future and transform the technology to a wide range of clinical and point-of-care applications.     

Determination of nitrite in saliva using microfluidic paper-based analytical devices

Point-of-care platforms can provide fast responses, decrease the overall cost of the treatment, allow for in-home determinations with or without a trained specialist, and improve the success of the treatment. This is especially true for microfluidic paper-based analytical devices (μPAD), which can enable the development of highly efficient and versatile analytical tools with applications in a variety of biomedical fields. The objective of this work was the development of μPADs to identify and quantify levels of nitrite in saliva, which has been proposed as a potential marker of periodontitis. The devices were fabricated by wax printing and allowed the detection of nitrite by a colorimetric reaction based on a modified version of the Griess reaction. The presented modifications, along with the implementation of a paper-based platform, address many of the common drawbacks (color development, stability, etc.) associated with the Griess reaction and are supported by results related to the design, characterization, and application of the proposed devices. Under the optimized conditions, the proposed devices enable the determination of nitrite in the 10–1000 μmol L⁻¹ range with a limit of detection of 10 μmol L⁻¹ and a sensitivity of 47.5 AU [log (μmol L⁻¹)]⁻¹. In order to demonstrate the potential impact of this technology in the healthcare industry, the devices were applied to the analysis of a series of real samples, covering the relevant clinical range.     

Lamination-based rapid prototyping of microfluidic devices using flexible thermoplastic substrates

Transposing highly sensitive DNA separation methods (such as DNA sequencing with high read length or the detection of point mutations) to microchip format without loss of resolution requires fabrication of relatively long (approx. 10 cm) microchannels along with sharp injection bands. Conventional soft lithography methods, such as mold casting or hot-embossing in a press, are not convenient for fabricating long channels. We have developed a lamination-based replication technique for rapid fabrication of sealed microfluidic devices with a 10 cm long, linear separation channel. These devices are fabricated in thin cyclo-olefin copolymer (COC) plastic substrates, thus making the device flexible and capable of assuming a range of 3-D configurations. Due to the good optical properties of COC, this new family of devices combines multiple advantages of planar microfluidics and fused-silica capillaries.     

Three-dimensional paper microfluidic devices assembled using the principles of origami

We report a method, based on the principles of origami (paper folding), for fabricating three-dimensional (3-D) paper microfluidic devices. The entire 3-D device is fabricated on a single sheet of flat paper in a single photolithographic step. It is assembled by simply folding the paper by hand. Following analysis, the device can be unfolded to reveal each layer. The applicability of the device to chemical analysis is demonstrated by colorimetric and fluorescence assays using multilayer microfluidic networks.     

Shape-controlled production of biodegradable calcium alginate gel microparticles using a novel microfluidic device

In this paper we describe a novel method of manufacturing shape-controlled calcium alginate gel microparticles in a microfluidic device. Both manufacturing shape-controlled microparticles and synthesizing hydrogel microparticles could be performed simultaneously in the microfluidic device. The novel microfluidic device comprised of two individual flow-focusing channels and a synthesizing channel was successfully applied as a continuous microfluidic reactor to synthesize gel microparticles with size and shape control. By passive control based on the microchannel geometric confinement and liquid-phase flow rates, we succeeded in producing monodisperse sodium alginate microparticles with diverse shapes (such as plugs, disks, microspheres, rods, and threads) in the flow-focusing channels of the microfluidic device. The shape and size of the sodium alginate microparticles could be tuned by adjusting the flow rates of the various streams. Further stages of the chemical reaction could be initiated by mixing sodium alginate microparticles and calcium chloride (CaCl2) solution in the synthesizing channel. The shapes of the sodium alginate microparticles could be permanently preserved by the synthesis of calcium alginate gel microparticles. The preparation conditions of size- and shape-controlled calcium alginate microparticles and influence factors were studied.     

Dynamic temperature measurement in microfluidic devices using thermochromic liquid crystals

Thermochromic liquid crystals (TLCs) are used to explore the temperature transients during thermal cycling for microchip-based polymerase chain reaction (PCR). By analyzing the reflected spectra of the TLCs over time, temperature vs. time trajectories were extracted and overshoots/undershoots were estimated. To our knowledge, this is the first report of TLC-based dynamic temperature measurements in a microfluidic device for all PCR temperature stages.     

Multiport flow-control system for lab-on-a-chip microfluidic devices

A multiport system suitable for pressure control on a lab-on-a-chip microfluidic device is described. An algorithm and a strategy for calculating pressures were developed to control the flow from multiple reservoirs for the microfluidic devices. Dye mixing and enzyme assay titration experiments were performed using pressure-driven flow only. Results show a good linear response over two orders of dynamic range.     

Monolithic media in microfluidic devices for proteomics

Considerable effort has been invested in the development of integrated microfluidic devices for fast and highly efficient proteomic studies. Among various fabrication techniques for the preparation of analytical components (separation columns, reactors, extractors, valves, etc.) in integrated microchips, in situ fabrication of monolithic media is receiving increasing attention. This is mainly due to the ease and simplicity of preparation of monolithic media and the availability of various precursors and chemistries. In addition, UV-initiated photopolymerization technique enables the incorporation of multiple analytical components into specified parts of a single microchip using photomasks. This review summarizes preparation methods for monolithic media and their application as microfluidic analytical components in microchips.     

Dissolution-guided wetting for microarray and microfluidic devices

The trapping of air bubbles presents a substantial impediment for the user in the increasingly widespread use of lab-on-a-chip products having microcavities in the forms of microwells, traps, dead ends and corners. Here we demonstrate a simple, effective, and passive method to eliminate air bubbles by coating hydrophilized microarray and microfluidic devices with a monosaccharide such as d-glucose or D-sorbitol, where the microcavities are filled with a conformal, elliptical, cone-shaped monosaccharide solid. These devices were stored in air for up to 6 months with a complete rewetting of the microcavities by dissolution of the monosaccharide with an aqueous solution.