Passive Mixing Capabilities of Micro- and Nanofibres When Used in Microfluidic Systems

Nanofibres are increasingly being used in the field of bioanalytics due to their large surface-area-to-volume ratios and easy-to-functionalize surfaces. To date, nanofibres have been studied as effective filters, concentrators, and immobilization matrices within microfluidic devices. In addition, they are frequently used as optical and electrochemical transduction materials. In this work, we demonstrate that electrospun nanofibre mats cause appreciable passive mixing and therefore provide dual functionality when incorporated within microfluidic systems. Specifically, electrospun nanofibre mats were integrated into Y-shaped poly(methyl methacrylate) microchannels and the degree of mixing was quantified using fluorescence microscopy and ImageJ analysis. The degree of mixing afforded in relationship to fibre diameter, mat height, and mat length was studied. We observed that the most mixing was caused by small diameter PVA nanofibres (450-550 nm in diameter), producing up to 71% mixing at the microchannel outlet, compared to up to 51% with polystyrene microfibres (0.8-2.7 p.m in diameter) and 29% mixing in control channels containing no fibres. The mixing afforded by the PVA nanofibres is caused by significant inhomogeneity in pore size and distribution leading to percolation. As expected, within all the studies, fluid mixing increased with fibre mat height, which corresponds to the vertical space of the microchannel occupied by the fibre mats. Doubling the height of the fibre mat led to an average increase in mixing of 14% for the PVA nanofibres and 8% for the PS microfibres. Overall, mixing was independent of the length of the fibre mat used (3-10 mm), suggesting that most mixing occurs as fluid enters and exits the fibre mat. The mixing effects observed within the fibre mats were comparable to or better than many passive mixers reported in literature. Since the nanofibre mats can be further functionalized to couple analyte concentration, immobilization, and detection with enhanced fluid mixing, they are a promising nanomaterial providing dual-functionality within lab-on-a-chip devices

Development of disposable carbon nanofibers electrodes supported on filters

Junta de Castilla yLeýn (GR71, BU349-U13) and the Ministerio de Economa yCompetitividad(CTQ2014-55583-R, CTQ2014-61914-EXP

Blend electrospinning of dye-functionalized chitosan and poly(ε-caprolactone) : towards biocompatible pH-sensors

Fast-response and easy-to-visualize colorimetric nanofibrous sensors show great potential for visual and continuous control of external stimuli. This makes them applicable in many fields, including wound management, where nanofibers serve as an optimal support material. In this paper, fast responding and user-friendly biocompatible, halochromic nanofibrous sensors are successfully fabricated by incorporating the halochromic dyes Methyl Red and Rose Bengal inside a chitosan/poly(e-caprolactone) nanofibrous matrix. The commonly applied dye-doping technique frequently suffers from dye-leaching, which not only reduces the sensor's sensitivity over time but can also induce adverse effects. Therefore, in this work, dye-immobilization is accomplished by covalent dye-modification of chitosan before blend electrospinning. It is shown that efficient dye-immobilization with minimal dye-leaching is achieved within the biomedical relevant pH-region, without significantly affecting the halochromic behavior of the dyes. This is in contrast to the commonly applied dye-doping technique and other dye-immobilization strategies stated in literature. Moreover, the nanofibers show high and reproducible pH-sensitivity by providing an instantaneous color change in response to change in pH in aqueous medium and when exposed to acidic or basic gases. The results stated within this work are of particular interest for natural (bio) polymers for which covalent modification combined with electrospinning provides a universal method for versatile dye-functionalization of large area nanofibrous membranes with proper dye-immobilization

Morphological traits essential to electrospun and grafted Nylon-6 nanofiber membranes for capturing submicron simulated exhaled breath aerosols

As contagious bio-aerosols continue to impact our society, we examine how the morphological traits of large-scale (15 cm x 93 cm), uniformly thick, electrospun Nylon membranes can contribute to the development of diagnostic, sensor driven face masks for capturing exhaled breath content. In our study, we compare the capture efficiencies of three types of large-scale Nylon-6 nanofiber membranes against those of commercial control textiles for capturing in-lab simulated salt breath aerosols. One of the electrospun membranes was also surface functionalized via grafting technique. The fabrication, functionalization, and exhaled aerosol capture of these large-scale membranes underscores the importance of assessing the lifetime, and usability, of electrospun materials before future integration with diagnostic sensing platforms can be successfully achieved

Colorimetric nanofibers as optical sensors

Sensors play a major role in many applications today, ranging from biomedicine to safety equipment, where they detect and warn us about changes in the environment. Nanofibers, characterized by high porosity, flexibility, and a large specific surface area, are the ideal material for ultrasensitive, fastresponding, and user-friendly sensor design. Indeed, a large specific surface area increases the sensitivity and response time of the sensor as the contact area with the analyte is enlarged. Thanks to the flexibility of membranes, nanofibrous sensors cannot only be applied in high-end analyte detection, but also in personal, daily use. Many different nanofibrous sensors have already been designed; albeit, the most straightforward and easiest-to-interpret sensor response is a visual change in color, which is of particular interest in the case of warning signals. Recently, many researchers have focused on the design of so-called colorimetric nanofibers, which typically involve the incorporation of a colorimetric functionality into the nanofibrous matrix. Many different strategies have been used and explored for colorimetric nanofibrous sensor design, which are outlined in this feature article. The many examples and applications demonstrate the value of colorimetric nanofibers for advanced optical sensor design, and could provide directions for future research in this area

Light-front holographic QCD and emerging confinement

In this report we explore the remarkable connections between light-front dynamics, its holographic mapping to gravity in a higher-dimensional anti-de Sitter (AdS) space, and conformal quantum mechanics. This approach provides new insights into the origin of a fundamental mass scale and the physics underlying confinement dynamics in QCD in the limit of massless quarks. The result is a relativistic light-front wave equation for arbitrary spin with an effective confinement potential derived from a conformal action and its embedding in AdS space. This equation allows for the computation of essential features of hadron spectra in terms of a single scale. The light-front holographic methods described here give a precise interpretation of holographic variables and quantities in AdS space in terms of light-front variables and quantum numbers. This leads to a relation between the AdS wave functions and the boost-invariant light-front wave functions describing the internal structure of hadronic bound-states in physical space-time. The pion is massless in the chiral limit and the excitation spectra of relativistic light-quark meson and baryon bound states lie on linear Regge trajectories with identical slopes in the radial and orbital quantum numbers. In the light-front holographic approach described here currents are expressed as an infinite sum of poles, and form factors as a product of poles. At large q(2) the form factor incorporates the correct power-law fall-off for hard scattering independent of the specific dynamics and is dictated by the twist. At low q2 the form factor leads to vector dominance. The approach is also extended to include small quark masses. We briefly review in this report other holographic approaches to QCD, in particular top-down and bottom-up models based on chiral symmetry breaking. We also include a discussion of open problems and future applications. (C)) 2015 Elsevier B.V. All rights reserved

Functionalized Electrospun Nanofibers In Microfluidic Bioanalytical Systems

Biosensors detect target analytes through specific binding with biological recognition elements such as nucleic acids, enzymes, and antibodies. Many labs are working to create inexpensive and portable miniaturized sensors that allow for rapid sample analysis and low reagent consumption in order to increase biosensor accessibility in rural areas and third world countries. Lab-on-a-chip devices aim to incorporate sample preparation and analyte detection into one device in order to create self-contained sensors that can be used in rural areas and third world countries where laboratory equipment may not be available. Often, these devices incorporate microfluidics in order to shorten reaction times, reduce handling of hazardous samples, and take advantage of laminar flow [1]. However, while several successful lab-on-achip devices have been developed, incorporating sample preparation and analyte detection within one device is still a key challenge in the design of many biosensors. Sample preparation is extremely important for miniaturized sensors, which have a low tolerance for sample impurities and particulates [1]. In addition, significant sample concentration is often required to reduce sample volumes to the nL to mL range used in miniaturized sensors. This research aims to address the need for sample preparation within lab-on-a-chip systems through the use of functionalized electrospun nanofibers within polymer microfluidic devices. Electrospinning is a fiber formation process that uses electrical forces to form fibers with diameters on the order of 100 nm from polymer spinning dopes [2, 3]. The non-woven fiber mats formed during electrospinning have extremely high surface area to volume ratios, and can be used to increase the sensitivity and binding capacity of biosensors without increasing their size. Additionally, the fibers can be functionalized through the incorporation of nano and microscale materials within a polymer spinning dope. In this work, positively and negatively charged v nanofibers were created through the incorporation of hexadimethrine bromide (polybrene) and poly(maleic anhydride) (Poly(MA)) within a poly(vinyl alcohol) spinning dope. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed the successful incorporation of polybrene and poly(MA) into the nanofibers. Gold microelectrodes were patterned on poly(methyl methacrylate) (PMMA) to facilitate the incorporation of nanofibers within microfluidic devices. The gold microelectrodes served as grounded collector plates during electrospinning and produced well-aligned nanofiber mats. Microchannels 1 mm wide and 52 [MICRO SIGN]m deep were imprinted into PMMA through hot embossing with a copper template. PMMA pieces embossed with microchannels were bonded to PMMA pieces with gold microelectrodes and nanofibers using UV-assisted thermal bonding. Positively charged polybrene-modified nanofibers were shown to successfully filter negatively charged fluorescent liposomes out of a HEPES-sucrose-saline buffer, while negatively charged poly(MA)-modified nanofibers were shown to repel the liposomes. The effect of nanofiber mat thickness on liposome retention was studied using the z-scan function of a Leica confocal microscope. It was determined that positively charged nanofibers exhibited optimal liposome retention at thicknesses of 20 [MICRO SIGN]m and above. Negatively charged nanofiber mats over 40 [MICRO SIGN]m thick retained liposomes due to their small pore size despite their surface charge. Finally, it was demonstrated that a HEPES-sucrose-saline solution of pH 8.5 could be used to change the charge of the positively charged polybrene nanofibers and allow for the release of previously bound liposomes. The results of this study can be used to design lab-on-a-chip devices capable of performing all sample preparation and analyte detection in one miniaturized microfluidic sensor. vi In addition, other nanofiber surface chemistries can be studied to create more specific sample filtration and allow for immobilization of biological recognition element. vi

Functionalized Electrospun Nanofibers For Sample Preparation And Analyte Detection In Microfluidic Bioanalytical Systems

Microfluidic biosensors which incorporate both sample preparation and analyte detection, also referred to as lab-on-a-chip (LOC) devices, are a promising means of providing low cost, rapid, and portable analyte detection in point-of-care, rural, and developing world applications1- 3 . However, despite numerous reports of LOC devices capable of detecting a range of clinical analytes1-3, there are several key challenges that face the development of true LOC devices. First, due to the small size of these miniaturized systems, it is often necessary to significantly concentrate the sample volume to the nL-[MICRO SIGN]L range 4. Additionally, samples must be purified to remove particulates and impurities that may impede analyte detection. Finally, fluid flow in microfluidic devices is generally laminar, which limits the amount of fluid mixing that occurs within the channels5-7. Because rapid fluid mixing is typically required to facilitate chemical reactions and ensure access of analytes to functional surfaces within the microchannels, micromixers need to be incorporated into the design of a LOC device. This research aims to address the need for both better sample preparation and fluid mixing within microfluidic assays through the use of functionalized electrospun nanofibers. Electrospinning is a fiber formation process in which electrical forces are used to form ultrathin fibers from viscous polymer spinning solutions8. The nonwoven fiber mats produced during electrospinning are characterized by extremely large surface-area-to-volume ratios and high porosities. Additionally, electrospun nanofibers can easily be functionalized either through the inclusion of nanoscale materials into the polymer spinning dope, or through post-spinning modifications. In this work, positively and negatively charged poly(vinyl alcohol) (PVA) nanofibers were created through the addition of hexadimethrine bromide (polybrene) and poly(methyl vinyl ether-alt-maleic anhydride) (poly(MVE/MA), respectively, into a 10% w/v PVA spinning solution. Additionally, larger diameter polystyrene (PS) microfibers with a range of morphologies were spun using 12.5, 15, and 17% w/v PS spinning solutions. Previously, gold microelectrodes patterned onto poly(methyl methacrylate) (PMMA) were used to incorporate the nanofibers into microfluidic channels9,10. However, in this work, fibers were bonded into microchannels without the use of a gold electrode, resulting in simple, inexpensive device fabrication. Both PVA and PS fibers were spun onto metal collector plates and manually transferred to pieces of PMMA that had undergone UV-Ozone treatment. In order to produce nanofiber mats with uniform fiber distributions along their height, thin nanofiber mats were stacked together to create multilayered mats 11,12. Positively charged PVA mats were shown to successfully bind and concentrate E. coli cells, while negatively charged PVA mats repelled the cells and were used to minimize nonspecific retention within the channels. The 3D morphology of the PVA nanofiber mats was optimized to eliminate nonspecific mechanical retention of the E. coli while also providing sufficient surface area for E. coli capture. Finally, anti-E. coli antibodies were immobilized on negatively charged PVA fibers to allow for successful specific capture of the analyte. Fluid mixing within Y-shaped microchannels was enhanced through the incorporation of both PVA nanofibers and PS microfibers, though the PVA fibers produced the most significant mixing. We assume that mixing within the PVA nanofiber mats is caused by the inhomogeneity of pore size and pore distribution within the mats rather than by the individual nanofibers. Statistical analysis of mixing within the nanofiber mats indicates that mixing is dependent on the height of the nanofiber mat (i.e. the number of layers) but is independent of the length of the nanofiber mat. As expected, the amount of mixing observed increased with decreasing fluid flow rate. The results of this study can be used to provide both enhanced sample preparation and fluid mixing with microfluidic biosensors. In addition, further functionalization of the nanofiber surfaces can be used to allow for detection of a wide range of analytes

Biologically Inspired Nanofibers for Use in Translational Bioanalytical Systems

Electrospun nanofiber mats are characterized by large surface-area-to-volume ratios, high porosities, and a diverse range of chemical functionalities. Although electrospun nanofibers have been used successfully to increase the immobilization efficiency of biorecognition elements and improve the sensitivity of biosensors, the full potential of nanofiber-based biosensing has not yet been realized. Therefore, this review presents novel electrospun nanofiber chemistries developed in fields such as tissue engineering and drug delivery that have direct application within the field of biosensing. Specifically, this review focuses on fibers that directly encapsulate biological additives that serve as immobilization matrices for biological species and that are used to create biomimetic scaffolds. Biosensors that incorporate these nanofibers are presented, along with potential future biosensing applications such as the development of cell culture and in vivo sensors