Theory, fabrication and applications of microfluidic and nanofluidic biosensors

Biosensors are a broad array of devices that detect the type and amount of a biological species or biomolecule. Several different types of biosensors have been developed that rely on changes to mechanical, chemical or electrical properties of the transduction or sensing element to induce a measurable signal. Often, a biosensor will integrate several functions or unit operations such as sample extraction, manipulation and detection on a single platform. This review begins with an overview of the current state-of-the-art biosensor field. Next, the review delves into a special class of biosensors that rely on microfluidics and nanofluidics by presenting the underlying theory, fabrication and several examples and applications of microfluidic and nanofluidic sensors.     

Low-temperature convector made from polymeric material for heat-pump applications

With a view to reducing the operating temperature of air heaters, a convector consisting of a plate heat-transfer matrix, placed at the bottom of an enclosure acting as a chimney, was designed and tested. An inexpensive polymeric material (polypropylene) was selected for the heat-transfer plates to achieve a lightweight low-cost unit. An appropriate computer program was used to optimize the prototype convector and to evaluate the influence of the main geometric and operational parameters: plate spacing and height; chimney height; heat carrier temperature and rate. The performance of the unit subsequently fabricated, measured in a thermostatic test chamber, was in good agreement with the theoretical predictions. As an example, an output of 1.2 kW was obtained for a mean water temperature of 41°C with a convector volume of 0.22 m³, two-thirds of which was occupied by the chimney. The convector exhibited a good thermal output even when fed at very low water rates, thus achieving a thorough cooling of the incoming water. The convector performance could be enhanced by resorting either to higher chimneys or to a mechanical draught. In the latter case, it is shown theoretically that a small fan's power consumption (say 5 W) is sufficient to at least double the natural convection output, provided the heat-transfer matrix is re-optimized.     

A nanofluidic railroad switch for DNA

We present a metamaterial consisting of a two-dimensional, asymmetric lattice of crossed nanochannels in fused silica, with channel diameters of 80 nm to 140 nm. When DNA is introduced, it is stretched and linearized. We show that the asymmetry in channel dimensions gives rise to a preferred direction for DNA orientation and a preferred direction for transport under dc electrophoresis. Interestingly, the preferred axis of orientation and transport can be switched by 90 degrees through application of an ac voltage. We explain the results in terms of an energy landscape for polyelectrolytes that consists of entropic and dielectrophoretic contributions and whose strength and sign can be tuned by changing the ac field strength.     

Tuneable elastomeric nanochannels for nanofluidic manipulation

Fluidic transport through nanochannels offers new opportunities to probe fundamental nanoscale transport phenomena and to develop tools for manipulating DNA, proteins, small molecules and nanoparticles. The small size of nanofabricated devices and the accompanying increase in the effect of surface forces, however, pose challenges in designing and fabricating flexible nanofluidic systems that can dynamically adjust their transport characteristics according to the handling needs of various molecules and nanoparticles. Here, we describe the use of nanoscale fracturing of oxidized poly(dimethylsiloxane) to conveniently fabricate nanofluidic systems with arrays of nanochannels that can actively manipulate nanofluidic transport through dynamic modulation of the channel cross-section. We present the design parameters for engineering material properties and channel geometry to achieve reversible nanochannel deformation using remarkably small forces. We demonstrate the versatility of the elastomeric nanochannels through tuneable sieving and trapping of nanoparticles, dynamic manipulation of the conformation of single DNA molecules and in situ photofabrication of movable polymeric nanostructures.     

Bio-inspired polymeric patterns with enhanced wear durability for microsystem applications

At micro/nano-scale, friction force dominates at the interface between bodies moving in relative motion and severely affects their smooth operation. This effect limits the performance of microsystem devices such as micro-electro-mechanical systems (MEMS). In addition, friction force also leads to material removal or wear and thereby reduces the durability i.e. the useful operating life of the devices. In this work, we fabricated bio-inspired polymeric patterns for tribological applications. Inspired by the surface features on lotus leaves namely, the protuberances and wax, SU-8 polymeric films spin-coated on silicon wafers were topographically and chemically modified. For topographical modification, micro-scale patterns were fabricated using nanoimprint lithography and for chemical modification, the micro-patterns were coated with perfluoropolyether nanolubricant. Tribological investigation of the bio-inspired patterns revealed that the friction coefficients reduced significantly and the wear durability increased by several orders. In order to enhance the wear durability much further, the micro-patterns were exposed to argon/oxygen plasma and were subsequently coated with the perfluoropolyether nanolubricant. Bio-inspired patterns with enhanced wear durability, such as the ones investigated in the current work, have potential tribological applications in MEMS/Bio-MEMS actuator-based devices.     

Novel low-molecular-weight hypromellose polymeric films for aqueous film coating applications

The concentration of hypromellose (HPMC) is known to significantly impact the viscosity of coating solutions. The purpose of this study was to determine the viscosity of novel low-molecular-weight (LMW) HPMC products as a function of polymer concentration. The mechanical properties and water vapor permeability of free films prepared from these novel LMW HPMC polymers were also determined and the results were compared with films prepared with conventional HPMC. Solutions of LMW and conventional HPMC 2910 and 2906 containing up to 40% polyethylene glycol (PEG) 400 were prepared and the viscosities were measured using a Brookfield viscometer. Solutions were then cast onto glass plates and stored at 30?C and 50% relative humidity until films were formed. A Chatillon digital force gauge attached to a motorized test stand was used to quantify the mechanical properties of the films, whereas water vapor permeabilities were determined according to the ASTM E96 M-05 water method. As expected, the novel LMW polymer solutions exhibited significantly lower viscosities than the conventional comparators at equivalent polymer concentrations. Film strength of the LMW materials was lower than films prepared from the conventional HPMC solutions, although this effect was not as evident for the HPMC 2906 chemistry. Increasing concentrations of the plasticizer resulted in decreased tensile strength and Young?s modulus and increased elongation as well as increased water vapor permeability, irrespective of polymer type. No statistical difference was found between the tensile strength to Young?s modulus ratios of the F chemistry LMW and conventional HPMC polymer films.     

A review on biodegradable polymeric materials for bone tissue engineering applications

Biodegradable polymer scaffolds have played a significant role in wide range of tissue engineering application such as bone scaffolds since the last decade. The aim of this article is to provide the comprehensive overview of biocompatible and biodegradable polymer materials and composite materials with their advantages and drawbacks in the application of biomaterial scaffolds, furthermore the properties and degradation criteria of the biomaterials are discussed in this review.     

Potential applications of polymeric microsphere suspension as subcutaneous depot for insulin

The objective of this investigation was to develop an injectable, depot-forming drug delivery system for insulin based on microparticle technology to maintain constant plasma drug concentrations over prolonged period of time for the effective control blood sugar levels. Formulations were optimized with two well-characterized biodegradable polymers namely, poly(DL-lactide-co-glycolide) and poly-epsilon-caprolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in streptozotocin-induced hypoglycemic rats. With a large volume of internal aqueous phase during w/o/w double emulsion solvent evaporation process and high molecular weight of the polymers used, we could not achieve high drug capture and precise control over subsequent release within the study period of 60 days. However, this investigation revealed that upon subcutaneous injection, the biodegradable depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain insulin injection. Preliminary pharmacokinetic evaluation exhibited steady plasma insulin concentration during the study period. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.     

Gateable nanofluidic interconnects for multilayered microfluidic separation systems

The extension of microfluidic devices to include three-dimensional fluidic networks allows complex fluidic and chemical manipulations but requires innovative methods to interface fluidic layers. Externally controllable interconnects, employing nuclear track-etched polycarbonate membranes containing nanometer-diameter capillaries, are described that produce hybrid three-dimensional fluidic architectures. Controllable nanofluidic transfer is achieved by controlling applied bias, polarity, and density of the immobile nanopore surface charge and the impedance of the nanocapillary array relative to the microfluidic channels. Analyte transport between vertically separated microchannels has three stable transfer levels, corresponding to zero, reverse, and forward bias. The transfer can even depend on the properties of the analyte being transferred such as the molecular size, illustrating the flexible character of the analyte transfer. In a specific analysis implementation, nanochannel array gating is applied to capillary electrophoresis separations, allowing selected separated components to be isolated for further manipulation, thereby opening the way for preparative separations at attomole analyte mass levels.     

Combined electrospray ionization-atmospheric pressure chemical ionization source for use in high-throughput LC-MS applications

Fast and accurate analytical methods are essential to keep pace with sample libraries produced from combinational chemistry and high-throughput biological screening. Many laboratories now use a combination of ionization techniques for the characterization of these samples, including atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI), and photoionization (PI). Data are shown here from the analysis of a compound collection plate containing a variety of sample structures. ESI will normally analyze around 80% of these samples, necessitating a source change to analyze a further 10%. In this work, we have developed a new combined ESI-APCI source (ESCi) for use in on-line HPLC applications. The combined source allows alternate on-line ESI and APCI scans with polarity switching within a single analysis. The ESCi source has been designed to be a simple replacement for the existing mass spectrometer interfaces. Each ionization method is optimized independently using separate tuning parameters. Instrument electronics can readily switch between the two ionization methods and polarities within normal interscan time periods. The new source has reduced the analysis time of sample plates by eliminating the need for a source hardware change, source optimization, and repeat analyses.     

Fabrication of a polymeric vertical microlens with the dip method

We have investigated a process based on the dip method to fabricate a polymeric vertical microlens (PVM). After the primary dip step, the PVM is formed by hanging the liquid SU-8 on a wall in virtue of the strong adhesive force and liquid cohesion. The microlens is then baked and exposed in ultraviolet light to further cross-link the negative photoresist SU-8 to enhance thermal stability and reliability. According to the experimental results, the radius of curvature of the fabricated vertical microlens varies from 120.8 to 34.2 microm, which relates to the dip depth or the thickness of the dipped pool. To characterize the PVM, an edge-emitting laser diode (lambda=1.31 microm) is then bonded onto the optical bench and a detector is utilized to observe the beam divergence with and without the lens insertion. Compared with an angle of 40.8 degrees without the microlens, the beam passing through a suitable PVM shows a vertical far-field angle of 3.32 degrees. Furthermore, the lens efficiency, approximately 83.4%, is also specified by the measurements.     

Characterization and bioactive properties of zirconia based polymeric hybrid for orthopedic applications

Zirconia is a transition metal oxide with current applications to orthopedic implants. It has been shown to up-regulate specific genes involved in bio-integration and injury repair. This study examines the effects of zirconia and polydimethylsiloxane (PDMS) hybrids on the proliferation and viability of human primary osteoblast and fibroblast cells. In this study, zirconia–PDMS hybrid coatings were synthesized using a modified sol gel process. The hybrid material was characterized using optical microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle analysis. This study demonstrates that Zr–PMDS surface materials display hydrophobic surface properties coupled with a preferential deposition of polymer near the surface. Primary osteoblast and fibroblast proliferation and viability on hybrid coated surfaces were evaluated via a rapid screening methodology using WST-1 and calcein AM assays. The cells were seed at 5,000 cells per well in 96-well plates coated with various composition of Zr–PDMS hybrids. The results showed increasing cell proliferation with increasing zirconia concentration, which peaked at 90 % v/v zirconia. Proliferation of osteoblasts and fibroblasts displayed similar trends on the hybrid material, although osteoblasts displayed a bi-phasic dose response by the calcein AM assay. The results of this current study show that Zr–PDMS may be used to influence tissue–implant integration, supporting the use of the hybrid as a promising coating for orthopedic trauma implants.     

Optimizing frequency-domain fluorescence lifetime sensing for high-throughput applications: photon economy and acquisition speed

The signal-to-noise ratio of a measurement is determined by the photon economy of the detection technique and the available photons that are emitted by the sample. We investigate the efficiency of various frequency-domain lifetime detection techniques also in relation to time-domain detection. Nonlinear effects are discussed that are introduced by the use of image intensifiers and by fluorophore saturation. The efficiency of fluorescence lifetime imaging microscopy setups is connected to the speed of acquisition and thus to the imaging throughput. We report on the optimal conditions for balancing signal-to-noise ratio and acquisition speed in fluorescence lifetime sensing.     

Poly(glycidyl methacrylate-acrylonitrile)-based polymeric electrolytes for dye-sensitized solar cell applications

Poly(glycidyl methacrylate-acrylonitrile) P(GMA-AN) copolymer was synthesized and used as a polymer electrolyte in dye-sensitized solar cells (DSSCs). P(GMA-AN)-based polymer electrolyte is obtained by adding 1-methyl-3-propylimidazolium iodide (PMII) as a room temperature ionic liquid (RTIL), tetrabutylammonium iodide (TBAI), iodide (I2) as the source of redox couple (I3(-)/I(-)) in order to improve the power conversion efficiency (PCE) by addition of optimized plasticizer contents such as ethylene carbonate (EC) and propylene carbonate (PC) in an acetonitrile solvent. These polymer electrolyte results revealed that more stable photovoltaic performance such as PCE of 4.97% with enhanced short-circuit current density (J(SC), 10.42 mA/cm2) and open circuit voltage (V(OC), 0.75 V) and fill factor (FF) of 0.63 under standard light intensity of 100 mW/cm2, irradiation of AM 1.5 sunlight. It is expected that these polymer electrolyte is an attractive alternative to liquid electrolytes for the fabrication of the long term stable DSSCs.     

Off-lattice Monte Carlo methods for coarse-grained models of polymeric materials and selected applications

This brief review presents a general introduction to the Monte Carlo simulation of coarse-grained models for flexible macromolecules under various conditions: from the solution to the melt, in the bulk as well as in geometries confined by walls etc. In the first part, the general concepts for the construction of such coarse-grained models for the simulation of cooperative phenomena in multi-chain systems and `technical' aspects of Monte Carlo simulations are discussed, as well as the limitations that this methodology still has to face. In the second part, typical applications are briefly reviewed, including the dynamics of chains adsorbed on surfaces or confined between plates, the scattering function from semidilute polymer solutions, and the formation of micelles from solutions of short block copolymers in the bulk and at the surface. Finally, a brief comparison to related but somewhat different approaches (Monte Carlo simulation of lattice models, Molecular Dynamics of bead-spring models) is given.     

Optically fabricated three dimensional nanofluidic mixers for microfluidic devices

This paper describes a simple technique for fabricating complex, but well defined, three-dimensional (3D) networks of nanoscale flow paths in the channels of microfluidic systems. Near field scanning optical measurements reveal the optics associated with the fabrication process and the key features that enable its application to the area of microfluidics. Confocal studies of microfluidic devices that incorporate 3D nanostructures formed using this approach show that they function as efficient passive mixing elements, particularly at low Reynolds numbers. This application and others such as separation and extraction inmicrofluidic total analysis systems or lab on a chip devices represent promising areas for 3D nanostructures of this general type.     

Sparse partial least-squares regression and its applications to high-throughput data analysis

The partial least-squares (PLS) method is designed for prediction problems where the number of predictors is larger than the number of training samples. PLS is based on latent components that are linear combinations of all of the original predictors, so it automatically employs all predictors regardless of their relevance. This will potentially compromise its performance, but it will also make it difficult to interpret the result. In this paper, we propose a new formulation of the sparse PLS (SPLS) procedure to allow both sparse variable selection and dimension reduction. We use the standard L₁-penalty and the unbounded penalty of [1]. We develop a computing algorithm for SPLS by modifying the nonlinear iterative partial least-squares (NIPALS) algorithm, and illustrate the method with an analysis of a cancer dataset. Through the numerical studies we find that our SPLS method generally performs better than the standard PLS and other existing methods in variable selection and prediction.     

Non-planar nanofluidic devices for single molecule analysis fabricated using nanoglassblowing

A method termed 'nanoglassblowing' is presented for fabricating integrated microfluidic and nanofluidic devices with gradual depth changes and wide, shallow nanochannels. This method was used to construct fused silica channels with out-of-plane curvature of channel covers from over ten micrometers to a few nanometers, nanochannel aspect ratios smaller than 2 × 10(-5):1 (depth:width), and nanochannel depths as shallow as 7?nm. These low aspect ratios and shallow channel depths would be difficult to form otherwise without collapse of the channel cover, and the gradual changes in channel depth eliminate abrupt free energy barriers at the transition from microfluidic to nanofluidic regions. Devices were characterized with atomic force microscopy (AFM), white light interferometry, scanned height measurements, fluorescence intensity traces, and single molecule analysis of double-stranded deoxyribonucleic acid (DNA) velocity and conformation. Nanochannel depths and aspect ratios formed by nanoglassblowing allowed measurements of the radius of gyration, R(g), of single λ?DNA molecules confined to slit-like nanochannels with depths, d, ranging from 11?nm to 507?nm. Measurements of R(g) as a function of d agreed qualitatively with the scaling law R(g)∝d(-0.25) predicted by Brochard for nanochannel depths from 36?nm to 156?nm, while measurements of R(g) in 11?nm and 507?nm deep nanochannels deviated from this prediction.     

Surface modification of poly(ethylene terephthalate) polymeric films for flexible electronics applications

The production of Flexible Electronic Devices (FEDs) by roll-to-roll large-scale manufacturing processes is a rapidly growing sector and the development of functional (inorganic and/or organic) thin layers onto flexible polymeric substrates represents one of the key issues for the low cost production of FEDs. However, the flexible substrates should meet advanced demands, as high optical transparency, high barrier properties and increased adhesion of the subsequent functional layers, which will have a major affect on their performance, efficiency and lifetime. Plasma treatment can be successfully employed for the improvement of the bonding structure and surface properties of flexible polymeric substrates. In this work, we report on the effect of Pulsed DC N⁺ ion bombardment using different ion energies, on the bonding structure, electronic and optical properties and surface nanotopography of Poly(Ethylene Terephthalate) (PET) substrates. For the investigation of the optical properties, we have used in-situ and real-time Spectroscopic Ellipsometry from the IR to Vis-farUV spectral region, in combination to advanced modeling procedures, whereas Atomic Force Microscopy has been employed for surface nanotopography investigation. As it has been found, the N⁺ bombardment leads to the appearance of new chemical bonds (C-N or C-O bonds in Φ-NH₂, Φ-NHR, C(O)-NHR, Φ-OH, or (CO)-OH), as well as partial disappearing of the C-O bond of ester group, on a surface layer of PET.