Showing papers on "Microfluidics published in 2009"

Droplet microfluidic technology for single-cell high-throughput screening

Abstract: We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.

Bonding of thermoplastic polymer microfluidics

Abstract: Thermoplastics are highly attractive substrate materials for microfluidic systems, with important benefits in the development of low cost disposable devices for a host of bioanalytical applications. While significant research activity has been directed towards the formation of microfluidic components in a wide range of thermoplastics, sealing of these components is required for the formation of enclosed microchannels and other microfluidic elements, and thus bonding remains a critical step in any thermoplastic microfabrication process. Unlike silicon and glass, the diverse material properties of thermoplastics opens the door to an extensive array of substrate bonding options, together with a set of unique challenges which must be addressed to achieve optimal sealing results. In this paper we review the range of techniques developed for sealing thermoplastic microfluidics and discuss a number of practical issues surrounding these various bonding methods.

The Synthesis and Assembly of Polymeric Microparticles Using Microfluidics

Abstract: The controlled synthesis of micrometer-sized polymeric particles bearing features such as nonspherical shapes and spatially segregated chemical properties is becoming increasingly important. Such particles can enable fundamental studies on self-assembly and suspension rheology, as well as be used in applications ranging from medical diagnostics to photonic devices. Microfluidics has recently emerged as a very promising route to the synthesis of such polymeric particles, providing fine control over particle shape, size, chemical anisotropy, porosity, and core/shell structure. This progress report summarizes microfluidic approaches to particle synthesis using both dropletand flow-lithography-based methods, as well as particle assembly in microfluidic devices. The particles formed are classified according to their morphology, chemical anisotropy, and internal structure, and relevant examples are provided to illustrate each of these approaches. Emerging applications of the complex particles formed using these techniques and the outlook for such processes are discussed.

Colloids and Surfaces A: Physicochemical and Engineering Aspects

Abstract: Keywords: Droplets Bubbles Microfluidics Encapsulation Emulsion a b s t r a c t In this paper, we emphasize our long series of experiments proving that the physical processes along fluid interfaces can be exploited for creating unusual fluidic objects. We report for the first time a couple of new fluidic objects so-called “liquid onions” and “mayonnaise” droplets. The study starts from the observation of antibubbles, exhibiting unstable liquid‐air‐liquid interfaces. We show that the lifetime of such a system has the same origin as floating/coalescing droplets on liquid surfaces. By analyzing such behaviours, we created droplets bouncing on a liquid bath. The methods and physical phenomena collected in this paper provide a basis for the development of a discrete microfluidics. Open questions are underlined, experimental challenges and future applications are proposed.

Ultrafast microfluidics using surface acoustic waves

Abstract: We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and microbioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1-10 cms velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel. If the flow is sufficiently quiescent, the nodes of the transverse standing wave that arises across the microchannel also allow for particle aggregation, and hence, sorting on nodal lines. In addition, the SAW also facilitates other microfluidic capabilities. For example, capillary waves excited at the free surface of a sessile drop by the SAW underneath it can be exploited for micronanoparticle collection and sorting at nodal points or lines at low powers. At higher powers, the large accelerations off the substrate surface as the SAW propagates across drives rapid destabilization of the drop free surface giving rise to inertial liquid jets that persist over 1-2 cm in length or atomization of the entire drop to produce 1-10 mum monodispersed aerosol droplets, which can be exploited for ink-jet printing, mass spectrometry interfacing, or pulmonary drug delivery. The atomization of polymerprotein solutions can also be used for the rapid synthesis of 150-200 nm polymerprotein particles or biodegradable polymeric shells in which proteins, peptides, and other therapeutic molecules are encapsulated within for controlled release drug delivery. The atomization of thin films behind a translating drop containing polymer solutions also gives rise to long-range spatial ordering of regular polymer spots whose size and spacing are dependent on the SAW frequency, thus offering a simple and powerful method for polymer patterning without requiring surface treatment or physicalchemical templating.

Surface acoustic wave (SAW) directed droplet flow in microfluidics for PDMS devices

Abstract: We direct the motion of droplets in microfluidic channels using a surface acoustic wave device. This method allows individual drops to be directed along separate microchannel paths at high volume flow rates, which is useful for droplet sorting.

Droplet-Based Microfluidic Systems for High-Throughput Single DNA Molecule Isothermal Amplification and Analysis

Abstract: We have developed a method for high-throughput isothermal amplification of single DNA molecules in a droplet-based microfluidic system. DNA amplification in droplets was analyzed using an intercalating fluorochrome, allowing fast and accurate “digital” quantification of the template DNA based on the Poisson distribution of DNA molecules in droplets. The clonal amplified DNA in each 2 pL droplet was further analyzed by measuring the enzymatic activity of the encoded proteins after fusion with a 15 pL droplet containing an in vitro translation system.

The Digital Revolution: A New Paradigm for Microfluidics

Abstract: The digital revolution has come to microfluidics. In digital microfluidics (DMF), discrete droplets are manipulated by applying electrical fields to an array of electrodes. In contrast to microchannels, in DMF each sample and reagent is individually addressable, which facilitates exquisite control over chemical reactions. Here, we review the state-of-the-art in DMF, with a discussion of device formats, actuation physics, and biological and non)biological applications. Along the way, we identify the key players in the field, and speculate on the advances and challenges that lie ahead. As with other fronts in the digital revolution, there have been and will be unexpected developments as DMF matures, but we posit that the future is bright for this promising technology.

Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates

Abstract: Point-of-care diagnostics will strongly benefit from miniaturization based on microfluidics because microfluidics integrate functions that can together preserve valuable samples and reagents, increase sensitivity of a test, and accelerate mass transport limited reactions. But a main challenge is to incorporate reagents into microfluidics and to make microfluidics simple to use. Here, we integrate microfluidic functional elements, some of which were developed earlier, and reagents such as detection antibodies (dAbs), capture antibodies (cAbs) and analyte molecules for making one-step immunoassays: the integrated device only requires the addition of sample to trigger a cascade of events powered by capillary forces for effecting a sandwich immunoassay that is read using a fluorescence microscope. The microfluidic elements comprise a sample collector, delay valves, flow resistors, a deposition zone for dAbs, a reaction chamber sealed with a polydimethylsiloxane (PDMS) substrate, and a capillary pump and vents. Parameters for depositing 3.6 nL of a solution of dAb on the chip using an inkjet are optimized and the PDMS substrate is patterned with analytes, which provide a positive control, and cAbs. Various storage conditions of the patterned PDMS are investigated for up to 6 months revealing that storage with a desiccant preserved at least 51% of the activity of the cAbs. C-reactive protein (CRP), a general inflammation and cardiac marker, is detected using this one-step chip using only 5 µL of human serum by measuring fluorescent signals from 30 × 100 µm2 areas of the PDMS substrate in the wet reaction chamber. The one-step chip can detect CRP at a concentration of 10 ng mL−1 in less than 3 min and below 1 ng mL−1 within 14 min. The work presented here may spur the adoption of fluorescence immunoassays using capillary driven microfluidics and PDMS substrates for point-of-care diagnostics.

Inertial microfluidics for continuous particle filtration and extraction

Abstract: In this paper, we describe a simple passive microfluidic device with rectangular microchannel geometry for continuous particle filtration. The design takes advantage of preferential migration of particles in rectangular microchannels based on shear-induced inertial lift forces. These dominant inertial forces cause particles to move laterally and occupy equilibrium positions along the longer vertical microchannel walls. Using this principle, we demonstrate extraction of 590 nm particles from a mixture of 1.9 μm and 590 nm particles in a straight microfluidic channel with rectangular cross-section. Based on the theoretical analysis and experimental data, we describe conditions required for predicting the onset of particle equilibration in square and rectangular microchannels. The microfluidic channel design has a simple planar structure and can be easily integrated with on-chip microfluidic components for filtration and extraction of wide range of particle sizes. The ability to continuously and differentially equilibrate particles of different size without external forces in microchannels is expected to have numerous applications in filtration, cytometry, and bioseparations.

Molecular momentum transport at fluid-solid interfaces in MEMS/NEMS: a review.

Abstract: This review is focused on molecular momentum transport at fluid-solid interfaces mainly related to microfluidics and nanofluidics in micro-/nano-electro-mechanical systems (MEMS/NEMS). This broad subject covers molecular dynamics behaviors, boundary conditions, molecular momentum accommodations, theoretical and phenomenological models in terms of gas-solid and liquid-solid interfaces affected by various physical factors, such as fluid and solid species, surface roughness, surface patterns, wettability, temperature, pressure, fluid viscosity and polarity. This review offers an overview of the major achievements, including experiments, theories and molecular dynamics simulations, in the field with particular emphasis on the effects on microfluidics and nanofluidics in nanoscience and nanotechnology. In Section 1 we present a brief introduction on the backgrounds, history and concepts. Sections 2 and 3 are focused on molecular momentum transport at gas-solid and liquid-solid interfaces, respectively. Summary and conclusions are finally presented in Section 4.

Soft inertial microfluidics for high throughput separation of bacteria from human blood cells

Abstract: We developed a new approach to separate bacteria from human blood cells based on soft inertial force induced migration with flow defined curved and focused sample flow inside a microfluidic device. This approach relies on a combination of an asymmetrical sheath flow and proper channel geometry to generate a soft inertial force on the sample fluid in the curved and focused sample flow segment to deflect larger particles away while the smaller ones are kept on or near the original flow streamline. The curved and focused sample flow and inertial effect were visualized and verified using a fluorescent dye primed in the device. First the particle behaviour was studied in detail using 9.9 and 1.0 µm particles with a polymer-based prototype. The prototype device is compact with an active size of 3 mm2. The soft inertial effect and deflection distance were proportional to the fluid Reynolds number (Re) and particle Reynolds number (Rep), respectively. We successfully demonstrated separation of bacteria (Escherichia coli) from human red blood cells at high cell concentrations (above 108/mL), using a sample flow rate of up to 18 µL/min. This resulted in at least a 300-fold enrichment of bacteria at a wide range of flow rates with a controlled flow spreading. The separated cells were proven to be viable. Proteins from fractions before and after cell separation were analyzed by gel electrophoresis and staining to verify the removal of red blood cell proteins from the bacterial cell fraction. This novel microfluidic process is robust, reproducible, simple to perform, and has a high throughput compared to other cell sorting systems. Microfluidic systems based on these principles could easily be manufactured for clinical laboratory and biomedical applications.

Janus particles templated from double emulsion droplets generated using microfluidics.

Abstract: We present a simple microfluidics-based technique to fabricate Janus particles using double-emulsion droplets as templates. Since each half of the particles is templated from a different immiscible fluid, this method enables the formation of particles from two materials with vastly different properties. The use of microfluidics affords excellent control over the size, morphology, and monodispersity of the particles.

Electrokinetically-Driven Microfluidics and Nanofluidics

Abstract: 1. Introduction and fundamental concepts 2. Classical equilibrium theory due to surface changes 3. Electroosmotic transport 4. Electrophoretic transport and separation 5. Field-induced dielectric polarization 6. DC nonlinear electrokinetics due to field-induced double layer polarization 8. Dielectrophoresis and electrorotation - double layer effects 9. Electrohydrodynamic atomization, electrospinning and discharge driven vortices.

PMMA/PDMS valves and pumps for disposable microfluidics

Abstract: Poly(methyl methacrylate) (PMMA) is gaining in popularity in microfluidic devices because of its low cost, excellent optical transparency, attractive mechanical/chemical properties, and simple fabrication procedures. It has been used to fabricate micromixers, PCR reactors, CE and many other microdevices. Here we present the design, fabrication, characterization and application of pneumatic microvalves and micropumps based on PMMA. Valves and pumps are fabricated by sandwiching a PDMS membrane between PMMA fluidic channel and manifold wafers. Valve closing or opening can be controlled by adjusting the pressure in a displacement chamber on the pneumatic layer via a computer regulated solenoid. The valve provides up to 15.4 µL s−1 at 60 kPa fluid pressure and seals reliably against forward fluid pressure as high as 60 kPa. A PMMA diaphragm pump can be assembled by simply connecting three valves in series. By varying valve volume or opening time, pumping rates ranging from nL to µL per second can be accurately achieved. The PMMA based valves and pumps were further tested in a disposable automatic nucleic acid extraction microchip to extract DNA from human whole blood. The DNA extraction efficiency was about 25% and the 260 nm/280 nm UV absorption ratio for extracted DNA was 1.72. Because of its advantages of inexpensive, facile fabrication, robust and easy integration, the PMMA valve and pump will find their wide application for fluidic manipulation in portable and disposable microfluidic devices.

A Continuous Flow Synthesis of Micrometer-Sized Actuators from Liquid Crystalline Elastomers

Abstract: Adv. Mater. 2009, 21, 4859–4862 2009 WILEY-VCH Verlag G T IO N Liquid crystalline elastomers (LCEs) are weakly crosslinked polymers that contain shape-anisotropic moieties (mesogens) that self organize into liquid crystalline phases. It was proposed by de Gennes in 1975 that these materials would undergo a shape change during the phase transition from the liquid crystalline to the isotropic state, if all mesogens were ordered into the same direction, forming a monodomain. The ability to change shape on application of a certain external stimulus led to the fabrication of actuators based on these ‘‘intelligent’’ materials. These are mainly macroscopic actuators, having sizes of millimeters or centimeters. However, in recent years there has been a growing interest in the preparation of micrometer sized actuators, as these are interesting for novel fields of science such as micromechanics and robotics. Here we present the use of a microfluidic setup to prepare monodisperse, monodomainic, and micrometer-sized liquid-crystalline elastomer beads that show a strong and rapid shape change of about 70% in length during the phase transition. We show that the particle size as well as the quality of the monodomain can be controlled by the operating parameters of the microfluidic setup. The key step in preparing LCE-based actuators is the overall orientation of the liquid crystalline director (ideally the formation of a monodomain) before the material is crosslinked. Methods used in the previous cited works are mainly the stretching of pre-crosslinked films, the drawing of fibers from a polymer melt and the use of electric or magnetic fields. All these methods have in common that they are complex multistep processes that are difficult to automate and not suitable for the continuous preparation of a large number of actuators. In addition, they are problematic for preparing samples in the micrometer size region. Using microfluidics on the other hand allows the continuous preparation of a large number of monodisperse micro-particles with a minimum of time and effort. In addition we argue, that the polymerization of the droplets while they are flowing through a tube increases the tendency of the mesogens to adopt a monodomainic director field configuration, thus giving the particles actuation properties. In our approach a liquid crystallinemonomer wasmixed with a crosslinker and a photoinitiator, melted into the isotropic phase and injected through a thin needle into a co-flowing stream of immiscible silicone oil. The resulting droplets were cooled into the liquid-crystalline phase and polymerized by irradiation with UV-light while flowing through a piece of thin tubing. To achieve this, we constructed a novel microfluidic setup, which is based on earlier works of Serra and Zhang. In this approach the mixing of monomer and continuous phase is carried out via a fused silica capillary in a T-junction. The main challenge for the new setup was temperature control. As all known LC-monomers are solid at room temperature, we placed the T-junction as well as the tube containing the monomer mixture in a heat bath, which was set above the monomer clearing temperature. Two syringe pumps were used, one providing the flow of the continuous phase, the other one for pushing a low viscous oil into the monomer tube, while also providing flow. An uplight microscope was used to observe droplet formation at the end of the needle. The tube containing the monomer droplets continued out of the heat bath and was rolled onto a hot plate with its temperature set to that of the liquid crystalline phase of the monomer. UV-light was shone on the tube, initiating radical polymerization and crosslinking inside the droplets in the LC-phase. Several aspects were considered for choosing an appropriate LC material for this project. Polymeric materials were excluded because their viscosities are too high to be pumped through thin capillaries while in melt. In order to induce an orientation of the mesogens, the material has to be processed (crosslinked) in the liquid crystalline phase, thus making the use of solvents to reduce viscosity impossible. Therefore we needed a monomer that was already liquid crystalline and could easily and rapidly be polymerized and crosslinked in the flow setup. In addition, a strong coupling between the mesogen and the resulting polymer is important, as this is a prerequisite for a strong shape change of the actuator. Finally, the transition temperature for the material must occur in a temperature range to which the whole reactor setup can be heated. The choice fell on a three-core mesogen with a polymerizable acrylate group attached laterally over a flexible spacer (see Fig. 1 for chemical structure), which was described earlier by Patrick Keller. It has a nematic phase between 72 and 98 8C and has been used for actuator applications before. For the preparation of crosslinked polymer particles this LC-monomer was mixed with 10mol % of hexanedioldiacrylate (chemical structure also in Fig. 1) and 2wt % of the photoinitiator Lucirin TPO. The mixture was melted and injected to the monomer tube of the setup. In a microfluidic setup the particle size is controlled mainly by two parameters: the viscosity of

General digital microfluidic platform manipulating dielectric and conductive droplets by dielectrophoresis and electrowetting

Abstract: A general digital (droplet-based) microfluidic platform based on the study of dielectric droplet manipulation by dielectrophoresis (DEP) and the integration of DEP and electrowetting-on-dielectric (EWOD) is reported. Transporting, splitting, and merging dielectric droplets are achieved by DEP in a parallel-plate device, which expands the fluids of digital microfluidics from merely being conductive and aqueous to being non-conductive. In this work, decane, hexadecane, and silicone oil droplets were successfully transported in a 150 microm-high gap between two parallel plates by applying a DC voltage above threshold voltages. Non-volatile silicone oil droplets with viscosities of 20 and 50 cSt were studied in more detail in parallel-plate geometries with spacings of 75 microm, 150 microm, and 225 microm. The threshold voltages and the required driving voltages to achieve droplet velocities up to 4 mm/s in the different circumstances were measured. By adding a dielectric layer on the driving electrodes of the tested parallel-plate device, a general digital microfluidic platform capable of manipulating both dielectric and conductive droplets was demonstrated. DEP and EWOD, selectively generated by applying different signals on the same dielectric-covered electrodes, were used to drive silicone oil and water droplets, respectively. Concurrent transporting silicone oil and water droplets along an electrode loop, merging water and oil droplets, and transporting and separating the merged water-in-oil droplet were performed.

Magnetic hydrogel nanocomposites as remote controlled microfluidic valves

Abstract: In recent years, hydrogels have attracted attention as active components in microfluidic devices. Here, we present a demonstration of remote controlled flow regulation in a microfluidic device using a hydrogel nanocomposite valve. To create the nanocomposite hydrogel, magnetic nanoparticles were dispersed in temperature-responsive N-isopropylacrylamide (NIPAAm) hydrogels. The swelling and collapse of the resultant nanocomposite can be remotely controlled by application of an alternating magnetic field (AMF). A ceramic microfluidic device with Y-junction channels was fabricated using low temperature co-fired ceramic (LTCC) technology. The nanocomposite was incorporated as a valve in one of the channels of the device. An AMF of frequency 293 kHz was then applied to the device and ON–OFF control on flow was achieved. A pressure transducer was placed at the inlet of the channel and pressure measurements were done for multiple AMF ON–OFF cycles to evaluate the reproducibility of the valve. Furthermore, the effect of the hydrogel geometry on the response time was characterized by hydrogels with different dimensions. Magnetic hydrogel nanocomposite films of different thicknesses (0.5, 1, 1.5 mm) were subjected to AMF and the kinetics of collapse and recovery were studied.

Electroporation of Cells in Microfluidic Droplets

Abstract: Droplet-based microfluidics has raised a lot of interest recently due to its wide applications to screening biological/chemical assays with high throughput. Despite the advances on droplet-based assays involving cells, gene delivery methods that are compatible with the droplet platform have been lacking. In this report, we demonstrate a simple microfluidic device that encapsulates cells into aqueous droplets and then electroporates the encapsulated cells. The electroporation occurs when the cell-containing droplets (in oil) flow through a pair of microelectrodes with a constant voltage established in between. We investigate the parameters and characteristics of the electroporation. We demonstrate delivering enhanced green fluorescent protein (EGFP) plasmid into Chinese hamster ovary (CHO) cells. We envision the application of this technique to high-throughput functional genomics studies based on droplet microfluidics.

Dual frequency dielectrophoresis with interdigitated sidewall electrodes for microfluidic flow-through separation of beads and cells

Abstract: This paper presents a novel design and separation strategy for lateral flow-through separation of cells/particles in microfluidics by dual frequency coupled dielectrophoresis (DEP) forces enabled by vertical interdigitated electrodes embedded in the channel sidewalls. Unlike field-flow-fractionation-DEP separations in microfluidics, which utilize planar electrodes on the microchannel floor to generate a DEP force to balance the gravitational force and separate objects at different height locations, lateral separation is enabled by sidewall interdigitated electrodes that are used to generate non-uniform electric fields and balanced DEP forces along the width of the microchannel. In the current design, two separate AC electric fields are applied to two sets of independent interdigitated electrode arrays fabricated in the sidewalls of the microchannel to generate differential DEP forces that act on the cells/particles flowing through. Individual particles (cells or beads) will experience DEP forces differently due to the difference in their dielectric properties. The balance of the differential DEP forces from the electrode arrays will position dissimilar particles at distinct equilibrium planes across the width of the channel. When coupled with fluid flow, this results in lateral separation along the width of the microchannel and the separated particles can thus be automatically directed into branched channel outlets leading to different reservoirs for downstream processing. In this paper, we present the design and analysis of lateral separation enabled by dual frequency coupled DEP, and cell/bead and cell/cell separations are demonstrated with this lateral separation strategy. With vertical interdigitated electrodes on the sidewall, the height of the microchannel can be increased without losing the electric field strength in contrast to other multiple frequency DEP devices with planar electrodes. As a result, populations of cells can be separated simultaneously instead of one by one to enable high-throughput sorting microfluidic devices.

Integration of plasmonic trapping in a microfluidic environment

Abstract: Near field generated by plasmonic structures has recently been proposed to trap small objects. We report the first integration of plasmonic trapping with microfluidics for lab-on-a-chip applications. A three-layer plasmo-microfluidic chip is used to demonstrate the trapping of polystyrene spheres and yeast cells. This technique enables cell immobilization without the complex optics required for conventional optical tweezers. The benefits of such devices are optical simplicity, low power consumption and compactness; they have great potential for implementing novel functionalities for advanced manipulations and analytics in lab-on-a-chip applications.

Valve-based flow focusing for drop formation

Abstract: Microfluidic devices can produce highly monodisperse drops at kilohertz rates using flow-focus drop formation. We use single-layer membrane valves to control, in real time, the dimensions of the flow-focus drop makers. This allows drop size and frequency to be controlled in real time and without adjusting flow rates.

Electrochemical biosensors at the nanoscale

Abstract: The general mechanism of chemical sensing is based on molecular recognition linked to different transduction strategies based on electrochemical, optical, gravimetric or thermal effects that can convert the signal to digital information. Electrochemical sensors support accurate, fast, and inexpensive analytical methods with the advantages of being easily embedded and integrated into electronics, and having the greatest potential impact in the areas of healthcare, environmental monitoring (e.g. electronic noses), food packaging and many other applications (E. Bakker and Y. Qin, Anal. Chem., 2006, 78, 3965).1 Nanoscale electrochemical biosensors offer a new scope and opportunity in analytical chemistry. The reduction in the size of electrochemical biosensors to nanoscale dimensions expands their analytical capability, allowing the exploration of nanoscopic domains, measurements of local concentration profiles, detection in microfluidic systems and in vivo monitoring of neurochemical events by detection of stimulated dopamine release (R. Kennedy, L. Huang, M. Atkinson and P. Dush, Anal. Chem., 1993, 65, 1882).2 This article reviews both state of art developments in electrochemical nanosensing, and the industrial outlook.

Multiple modular microfluidic (M3) reactors for the synthesis of polymer particles

Abstract: We report a study of the continuous generation of polymer particles in parallel multiple modular microfluidic (M3) reactors. Each module consisted of sixteen parallel microfluidic reactors comprising emulsification and polymerization compartments. We identified and minimized the effects of the following factors that could result in the broadening of the distribution of sizes of the particles synthesized in the M3 reactors, in comparison with an individual microfluidic reactor: (i) the fidelity in the fabrication of multiple microfluidic droplet generators; (ii) the crosstalk between parallel droplet generators sharing liquid supply sources; and (iii) the coalescence of precursor droplets and/or partly polymerized polymer particles. Our results show that the M3 reactors can produce polymer microgel particles with polydispersity not exceeding 5% at a productivity of approximately 50 g/h.

Hybrid microfluidics: a digital-to-channel interface for in-line sample processing and chemical separations.

Abstract: Microchannels can separate analytes faster with higher resolution, higher efficiency and with lower reagent consumption than typical column techniques. Unfortunately, an impediment in the path toward fully integrated microchannel-based labs-on-a-chip is the integration of pre-separation sample processing. Although possible in microchannels, such steps are challenging because of the difficulty in maintaining spatial control over many reagents simultaneously. In contrast, the alternative format of digital microfluidics (DMF), in which discrete droplets are manipulated on an array of electrodes, is well-suited for carrying out sequential chemical reactions. Here, we report the development of the first digital-channel hybrid microfluidic device for integrated pre-processing reactions and chemical separations. The device was demonstrated to be useful for on-chip labeling of amino acids and primary amines in cell lysate, as well as enzymatic digestion of peptide standards, followed by separation in microchannels. Given the myriad applications requiring pre-processing and chemical separations, the hybrid digital-channel format has the potential to become a powerful new tool for micro total analysis systems.

Dilution-Free Analysis from Picoliter Droplets by Nano-Electrospray Ionization Mass Spectrometry

Abstract: The expanding role of microfluidics for chemical and biochemical analysis is due to factors including the favorable scaling of separation performance with reduced channel dimensions,[1] flexibility afforded by computer-aided device design, and the ability to integrate multiple sample handling and analysis steps into a single platform.[2] Such devices enable smaller liquid volumes and sample sizes to be handled than can be achieved on the benchtop, where sub-microliter volumes are difficult to work with and where sample losses to the surfaces of multiple reaction vessels become prohibitive. A particularly attractive microfluidic platform for sample-limited analyses employs aqueous droplets or plugs encapsulated by an immiscible oil.[3,4] Each droplet serves as a discrete compartment or reaction chamber enabling, e.g., high throughput screening[5,6] and kinetic studies[7-9] of femto- to nanoliter samples, as well as the encapsulation[10-12] and lysis[10] of individual cells with limited dilution of the cellular contents

Electrowetting control of Cassie-to-Wenzel transitions in superhydrophobic carbon nanotube-based nanocomposites

Abstract: The possibility of effective control of the wetting properties of a nanostructured surface consisting of arrays of amorphous carbon nanoparticles capped on carbon nanotubes using the electrowetting technique is demonstrated. By analyzing the electrowetting curves with an equivalent circuit model of the solid/liquid interface, the long-standing problem of control and monitoring of the transition between the "slippy" Cassie state and the "sticky" Wenzel states is resolved. The unique structural properties of the custom-designed nanocomposites with precisely tailored surface energy without using any commonly utilized low-surface-energy (e.g., polymer) conformal coatings enable easy identification of the occurrence of such transition from the optical contrast on the nanostructured surfaces. This approach to precise control of the wetting mode transitions is generic and has an outstanding potential to enable the stable superhydrophobic capability of nanostructured surfaces for numerous applications, such as low-friction microfluidics and self-cleaning.