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FEATURE ARTICLE www.rsc.org/materials | Journal of Materials Chemistry Material encapsulation and transport in core–shell micro/nanofibers, polymer and carbon nanotubes and micro/nanochannels A. L. Yarin,*a E. Zussman,b J. H. Wendorffc and A. Greinerc Received 18th December 2006, Accepted 30th March 2007 First published as an Advance Article on the web 24th April 2007 DOI: 10.1039/b618508h In this article, we review recent work on the co-electrospinning of polymer core–shell nanofibers and the manufacture of hollow nanotubes. The encapsulation and release of bioactive compounds from co-electrospun core–shell fibers is considered next, bearing in mind such applications as sensors and drug release. Then, nanofluidic phenomena in nanotubes made via co-electrospinning (as well as via the other processes) are discussed. We also consider dielectrophoresis in microchannels as a possible tool for the separation of viruses, nanoparticles and macromolecules. I Introduction Electrospinning of polymer nanofibers is part of the field of polymer solution electrohydrodynamics.1 The technique has attracted significant attention in the last decade, since it allows for a straightforward, relatively easy and cheap method of manufacturing polymer nanofibers. The process involves interesting physical phenomena and the resulting nanofibers are expected to find numerous practical applications because of their huge surface area, length, physical properties and relative ease of chemical and biological functionalization. Recently, a new branch of electrospinning, named co-electrospinning, emerged.2 Co-electrospinning allows for the manufacture of core–shell nanofibers. This process leads to encapsulation of the core material (not necessarily polymeric) which is potentially beneficial for the storage and drug delivery a Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, IL 60607-7022, USA. E-mail: [email protected] b Faculty of Mechanical Engineering-Israel Institute of Technology, Haifa 32000, Israel c Department of Chemistry and Center of Material Science, PhilippsUniversity Marburg, Germany Dr Alexander Yarin received his PhD and Habilitation in physics and mathematics from the Institute for Problems in Mechanics of the USSR Academy of Sciences. He was a professor at the Israel Institute of Technology (Technion). At present he is a professor at the University of Illinois at Chicago. His research interests include the hydrodynamics of flows with free surfaces (jets, films and droplets), rheology and hydrodynamics of non-Newtonian Alexander Yarin (e.g. polymeric) liquids, combustion and nanotechnology. Currently his research activities are centered on electrospinning and co-electrospinning of polymer This journal is ß The Royal Society of Chemistry 2007 of bioactive agents. A single-step post-processing of core–shell fibers allows one to dispense with a core if a hollow nano- or microtube is needed. At the same post-processing step, the shell material can be carbonized or calcinated. The resulting nano- and microtubes are unique in their length—which might reach several centimeters. The length of the tubes made via co-electrospinning allows their easy manipulation and integration in nano- and microdevices. Nano- and microfluidics in such devices is challenging and promises the manipulation, orientation and segregation of macromolecules, proteins, viruses, bacteria and other microscopic objects. In the present article we review the current state of the art of the co-electrospinning process and post-processing of core– shell fibers and hollow tubes (section II). The encapsulation and release of biologically active agents in core–shell fibers and their possible application for drug release and sensors are discussed in section III. Liquid transport and manipulation of particulates inside polymer and carbon nanotubes are considered in section IV. The general idea and design of a microchannel-based device, dielectrophoretic quadrupole lens, DQL, is outlined in sections V and VI. In the following sections, DQL operation and efficacy are analysed. In particular, the dielectrophoretic diffusion equation is derived nanofibers and their applications, suspensions and emulsions of nanoparticles, nanofluidics and coating of nanoparticles in lowpressure plasma. Dr Eyal Zussman is a professor at the Department of Mechanical Engineering at the TechnionIsrael Institute of Technology. He received his DSc degree in Mechanical Engineering from the Technion. He worked as a post-doctoral associate at the Technical University of Berlin, Eyal Zussman Germany. Dr Zussman’s main areas of research are nanotechnology and polymer processing, electrospinning, nano-assembly and material characterization. J. Mater. Chem., 2007, 17, 2585–2599 | 2585 in section VII. Based on it, the mass transfer of the dielectrophoretic particles (e.g., viruses) through the interface is described in section VIII. The numerical estimates in section IX show that under realistic conditions DQL can enhance the interfacial mass flux by a factor of 100. Conclusions are drawn, as well as perspectives are discussed, in section X. The main aim of the present article is in the exposition of the whole spectrum, beginning from the technological and scientific aspects of manufacturing of long nano- and microchannels with encapsulated biologically active agents inside, to fluidic manipulation, transport and release in the existing and potential nano- and microfluidic devices. The article reviews the existing literature, as well as contains a number of the original, as yet unpublished results. The latter are discussed in full detail. II Co-electrospinning of core–shell polymer micro/ nanofibers and manufacturing nanotubes 1 Advanced techniques, such as electrospinning and co-electrospinning,2 have recently been established to yield nanofibers and core–shell fibers from natural and synthetic polymers with diameters as small as a few nanometers. In addition, core–shell fibers can be produced via post-treatment of monolithic electrospun nanofibers used as templates. A polymer shell can be deposited via chemical vapor deposition, CVD3 (tubes by a fiber template process—TUFT), whereas metal shells can be either deposited by electroless plating,4a,b or sputtering.4c If needed, the third stage, heat treatment, is used to eliminate the template core and make hollow nanotubes. On the other hand, co-electrospinning allows single-step formation of core–shell fibers, whereas hollow tubes can be obtained at the second stage: heat treatment or chemical withdrawal. Co-electrospinning allows encapsulation of catalytic and magnetic nanoparticles, chromophores, enzymes, proteins and cell growth factors directly during the process.5 In co-electrospinning, a syringe with two compartments containing different polymer Dr Joachim Wendorff received his PhD in physics from the Philipps-Universität Marburg, Germany. He was a postdoc at the University of Massachusetts, Amherst, USA and received his Habilitation from the University of Mainz, Germany. He is a professor at Philipps-Universität Marburg, Germany. His research interests include polymers and polymer hybrids in nanotechnology, in particular: fibers, tubes and rods, preparation techniques Joachim Wendorff and applications; polymers for medical applications: tissue engineering, surface modification of implants, drug delivery; opto-electronic properties of low molar mass and polymer liquid crystals and functional polymers; structure and properties of polymer blends, polymer interfaces and ordered glasses; computer modelling. 2586 | J. Mater. Chem., 2007, 17, 2585–2599 Fig. 1 A double-compartment plastic syringe for co-electrospinning features separate supplies of core and shell materials. E 2003 WileyVCH. Used with permission. solutions or a polymer solution (shell) and a non-polymeric liquid or powder (core) is used to initiate a core–shell jet (Fig. 1). At the exit of the core–shell needle attached to the two-compartment syringe appears a core–shell droplet. Being subjected to a sufficiently strong electric field, it issues a compound jet, which undergoes the electrically-driven bending instability characteristic of the ordinary electrospinning process.1 Strong jet stretching, resulting from the bending instability, is accompanied by enormous jet thinning and rapid solvent evaporation, with solidified core–shell nanofibers depositing on a counter-electrode. Compound nanofibers co-electrospun from PSU–PEO [poly(sulfone)–poly(ethylene oxide)] solutions had an outer diameter on the order of 60 nm, a core diameter of about 40 nm and a relatively smooth core–shell interface, as apparent from Dr Andreas Greiner received his PhD and Habilitation in chemistry from PhilippsU n i v e r s i t a¨ t M a r b u r g , Germany. He was a postdoc at the University of California, Santa Barbara, USA. At present he is a professor at Philipps-Universität Marburg, Germany. His research interests include: monomer and polymer synthesis, functional polymers, metal catalysis of polymerizations, modern reaction techniques (vapor phase Andreas Greiner deposition polymerizations, microreaction, microwave), structure–property relationships of polymers, designed polymer morphologies by controlled polymerizations, liquid crystalline polymers, confinement structures (carbon nanotubes, polymer nanotubes, and polymer nanofibers), polymers for medical, optical, and microelectronic applications and sensors, advanced polymer processing techniques (CVD, electrospinning, TUFT, and WASTE-process). This journal is ß The Royal Society of Chemistry 2007 Fig. 2 TEM micrograph of a core–shell nanofiber. The core and shell solutions are PSU and PEO, respectively. E 2003 Wiley-VCH. Used with permission. Fig. 2. The co-electrospinning process is very versatile and is already fostering new materials design. In ref. 2a a 2 wt% solution of PEO in chloroform and a 1 wt% solution of PDT, poly(dodecylthiophene), in chloroform were co-electrospun as shell and core, respectively (Fig. 3). The total fiber diameters were about 1000 nm, whereas the diameters of the core region were about 200 nm. It is important to stress that the PDT used in these experiments did not form fibers by itself in electrospinning, due to its low molecular weight being effectively nonspinnable. However, fibers encapsulating PDT were obtained by co-electrospinning, since the PEO shell served as a template for the formation of PDT fibers. Co-electrospinning can also be applied to polymer/metal salt systems. A 3 wt% PLA, poly(L-lactide), chloroform solution was co-electrospun as a shell with a 5 wt% solution of Pd(OAc)2 in tetrahydrofurane as a core. In order to generate metalization, the core–shell fibers were annealed for 2 hours at 170 uC which caused conversion of Pd(OAc)2 in the core into elemental Pd (Fig. 4). The outer diameter of the coaxial fibers was about 500 nm and the Fig. 3 TEM micrograph of co-electrospun PEO (shell) and PDT (core) fiber. E 2003 Wiley-VCH. Used with permission. This journal is ß The Royal Society of Chemistry 2007 Fig. 4 TEM micrograph of an annealed sample of co-electrospun (PLA) and Pd(OAc)2. E 2003 Wiley-VCH. Used with permission. diameter of the core phase was about 60 nm. Pd(OAc)2 is non-spinnable and does not form fiber-like structures upon electrospinning. However, fiber-like structures can be obtained by co-electrospinning with PLA as a shell, which results in the one-dimensional arrangement of Pd. It is of particular interest that non-electrospinnable materials like PDT and Pd(OAc)2 can be forced into one-dimensional arrangements by coelectrospinning using a good fiber-forming shell polymer. As mentioned before, co-electrospinning yields a two-stage method of fabrication of hollow nanofibers (nanotubes) instead of the previously-used three-stage approach.3 In such a process, co-electrosopinning is followed by a selective removal of the core material in the core–shell fiber via selective solvents or heat treatment at the second stage. Calcination and pyrolysis of the electrospun sol–gel solutions or polymers containing metal atoms in the shell transform nanotubes into ceramic, silica and metal ones.2c,3c,6 Preparation of organic– inorganic materials, semiconductor systems which are functionalized by a structuring process taking place on the submicrometer scale is a promising goal of the co-electrospinning process7. Manufacturing of structured yet compact polymer fibers with diameters down to less than ten nanometers is also of significant interest. A two-stage technique for producing turbostratic carbon nanotubes via co-electrospinning of two polymer solutions— PMMA [poly(methylmethacrylate); core] and PAN [poly(acrylonitrile); shell] was introduced in ref. 8. The core capillary was a stainless steel needle with inner and outer diameters of 0.42 and 0.64 mm, respectively. The shell capillary was a plastic needle with inner and outer diameters of 1.2 and 1.75 mm, respectively. The tip of the core capillary protruded 0.3 to 1 mm below that of the shell capillary. During coelectrospinning, the solutions were subjected to an electrostatic field of about 0.3 kV cm21, and the as-spun core–shell nanofibers were collected on an aluminium foil that was placed 18 cm below the tip of the core needle. The carbonization process was carried out as follows: the as-spun core–shell nanofibers were placed on alumina substrates in a tube furnace and stabilized in air for 30 min at 250 uC, which resulted in thermal decomposition of the PMMA core. The fibers were J. Mater. Chem., 2007, 17, 2585–2599 | 2587 Fig. 6 Optical image of core–shell fibers, with an outer fiber diameter of around 7 mm and a core diameter of about 2–3 mm. E 2006 WileyVCH. Used with permission. Fig. 5 Flow pattern in the compound droplet attached to the core– shell spinneret with PAN solution (shell) and PMMA solution dyed with malachite green (core). The protruding core nozzle is visible. E 2006 Wiley-VCH. Used with permission. then carbonized by heating in nitrogen, first at 750 uC for 1 h, and then at 1100 uC for another hour. The ramp rate was 5 uC min21 between the 250, 750 and 1100 uC plateaus. Fig. 5 shows the typical pattern of the co-electrospinning process close to the core–shell spinneret. The core polymer capillary protrudes below the shell capillary. As can be seen, the core liquid experiences a sudden increase in diameter upon exiting the capillary tube, which may be attributed to the die swell effect. Below the point of maximum swelling, the outer solution forms a thin shell that attaches to the core polymer stream. The as-spun core–shell PMMA–PAN fibers are shown in Fig. 6. Subsequently, the collected as-spun fibers were stabilized in air at 250 uC and then heated in stages to 1100 uC in an inert nitrogen atmosphere as described above. PMMA in the core was completely thermally degraded which made the core hollow, whereas PAN in the shell carbonized, forming a turbostratic carbon structure.8,9 Fig. 7 shows an SEM images of several broken carbonized PAN fibers. These images clearly demonstrate the formation of hollow tubular structures. The average inner diameter is 500 nm (STD = 100 nm) and the average wall thickness is 200 nm (STD = 50 nm). The core channel is approximately concentric with the shell, with the occasional offset probably resulting from core buckling during the initial formation of the as-spun fibers. Fig. 7d shows a SEM image of a sample which was collected as a uniaxiallyaligned array using the electrostatic lens technique proposed in ref. 10. The average fracture strength of turbostratic carbon is 0.64 GPa, which shows that the nanotubes are rather strong. These strong carbon nanotubes can be produced with lengths of about 1 to 10 cm, while still maintaining submicron inner and outer diameters. The ordered arrays of turbostratic carbon nanotubes similar to the one in Fig. 7d can be used for membrane manufacturing. Another advantage of this process8 is that it does not involve the more elaborate sol–gel Fig. 7 (a–c) SEM images of fractured surfaces of single carbonized hollow nanofibers, (d) Aligned array of carbonized hollow nanofibers. E 2006 Wiley-VCH. Used with permission. 2588 | J. Mater. Chem., 2007, 17, 2585–2599 This journal is ß The Royal Society of Chemistry 2007 Fig. 8 Turbostratic carbon nanotubes made via co-electrospinning. In all the monolithic fibers with no channel seen in the cross-section the core material has not been entrained into the jet, which is a technological drawback. E 2006 American Institute of Physics. Used with permission. procedures usually required for manufacturing of ceramic nanofibers. Because of their unique characteristics, carbon nanotubes can be used in numerous applications in medicine (e.g., for drug delivery), for hydrogen storage with high uptake,11 in microelectronics (as molecular wires, diodes, field-effect transistors and single-electron transistors)12 and for development of fiber-reinforced materials to meet demanding weight and strength requirements. The analysis of the thermally treated nanotubes has shown that in several cases the original nanofibers do not possess a core–shell structure. For example, Fig. 8 shows the turbostratic carbon nanotubes where the PMMA core was removed using heat treatment in the post-processing step. Many nanotubes are hollow, but several nanotubes in Fig. 8 are monolithic and show no hollow structure. Apparently, the core solution (PMMA) in these cases had not been entrained into the shell (PAN), thus producing monolithic fibers. Fig. 8 visually displays the major challenge faced by co-electrospinning, namely the ultimate quality of the fiber sample. Both experimental and theoretical results8,13 show that formation of core–shell jets and nanotubes via co-electrospinning is greatly facilitated when the core nozzle protrudes outside the shell nozzle by around 50% of radius of the latter (cf. Fig. 5). Recently, it was found that 50/50 by weight blends of PMMA and PAN in DMF are unstable and in about a day transform into emulsions of 100 mm PMMA–DMF droplets in a PAN–DMF matrix. Electrospinning of such emulsions from a single nozzle results in PMMA–PAN core–shell fibers.14a A PMMA droplet sucked through the tip of the PAN Taylor cone is stretched to length of about 1 m. Therefore, the core in such fibers has practically no defects related to the switch from one PMMA–DMF droplet to another. Being carbonized, core–shell fibers electrospun from a single nozzle yield carbon nanotubes similar to those produced via co-electrospinning from the core–shell nozzle described above. It was noted that blends of PMMA and PAN in DMF in other proportions should result in multi-core nanofibers.14a Indeed, the latter have been obtained when such emulsions were electrospun from a single nozzle.14b,c Carbonization of the resulting fibers, yielded multi-channel carbon tubes. Significant simplification of co-electrospinning to a single nozzle process, happened at the same time when the opposite limit was tackled, namely co-electrospinning from a bundle of parallel nozzles located inside an outer envelope nozzle.14d After a post-processing calcination stage, this technique resulted in 3- to 5-channel ceramic tubes. This journal is ß The Royal Society of Chemistry 2007 The question whether solvents in core and shell solutions in co-electrospinning should be miscible or immiscible was discussed in ref. 2 and 6c. While the first works on coelectrospinning used miscible (in fact, identical) solvents in the core and shell, in some others claims were made that the process can be stabilized only when the solvents are immiscible. This question was recently re-examined,15 and it was shown that both miscible and immiscible solvents allow for an uninterrupted co-electrospinning process, while in the as-spun fibers the core–shell boundary is sharper when solvents are immiscible. Experiments show that under appropriate conditions, the solvent rapidly evaporates through the polymer network that constitutes the nanofibers undergoing electrospinning. As a result, hollow nanofibers emerge.15,16 Coelectrospun fibers can be also made hollow if the polymer concentration in the core is very low, whereas volatile solvent from the core evaporates through nanopores and other defects in the outer shell.15 Such hollow polymer tubes are subject to a pressure difference, with the atmospheric pressure outside being higher that the one inside. Then, the hollow tubes can completely collapse, resulting in ribbons16 (which approximately correspond to the elliptic shapes), or acquire complicated non-circular crosssectional shapes.15 The Young’s modulus of the nanotube walls can be easily determined from the photographs of their collapsed shapes. Indeed, the well-known expression for the critical external pressure qcr leading to a non-circular collapse of a pipe17 Eh3 n2 {1 (1) qcr ~ 12a3 ð1{n2 Þ can be employed. In the present case qcr = Dpcr, which is the pressure drop at the nanotube wall, Dpcr # l atm. Young’s modulus is denoted by E, Poisson’s ratio n should be taken equal to 1/2, since polymers can be roughly assumed to be incompressible. The tube wall thickness is denoted by h, and the cross-sectional radius of the hollow tube before collapse is denoted by a. The azimuthal wave-number n corresponds to collapse patterns seen on the photographs. For example, for flattened (elliptical) cross-sections n = 2 and eqn (1) yields E~ 3q3 Dpcr h3 (2) Taking Dpcr = l atm = 105 Pa and a/h = 10, we obtain E = 3 6 108 Pa = 0.3 GPa, which is comparable with the values of Young’s modulus for polymers (known to be of the order of 1 GPa). III Encapsulation and release of bioactive agents from core–shell nanofibers A number of bioactive agents have already been encapsulated in nanofibers (or could be potentially encapsulated). These include drugs, proteins and enzymes, and the release rates of different molecular compounds from electrospun and co-electrospun fibers have been studied in a number of experiments.18 As basic polymers for electrospinning and coelectrospinning (of the shell) for biomedical applications use is J. Mater. Chem., 2007, 17, 2585–2599 | 2589 typically made of solutions of biocompatible, sufficiently stable polymers with mechanical properties in the solid state comparable with those of soft tissues, for example PCL [poly(caprolactone)]. Several possible methods can be, in principle, employed to make monolithic and core–shell nanofibers with embedded bioactive agents. They are the following: (i) Host/guest electrospinning of monolithic nanofibers An aqueous solution of a bioactive agent is mixed with a polymer and electrospun as nanofibers. In this method, a spinnable polymer solution plays the role of the host, whereas a non-spinnable solution of a bioactive agent is the guest. In many cases a non-aqueous polymer solution is a must. Then, the resulting nanofibers will contain water inclusions with a bioactive agent.19a The main question here is whether the embedded bioactive agent will survive the electrospinning process and retain its biological properties after encountering non-aqueous solvents. Some results indicate that there are cases where the bioactivity of proteins is not altered by contact with various solvents during electrospinning. For example, bacteriorhodopsin, enzymes (e.g., bovine serum albumin), and albumin conjugated with fluorescein isothiocyanate were successfully immobilized in the electrospun nanofibers and retained their activity.5 Electrospun biopolymers, such as collagen types I, II and III, fibrinogen, elastin and chitosan,19b,c,d also retained bioactivity and have gained a great deal of attention because they can be used to fabricate biomimetic scaffolds for tissue engineering or wound dressing. Human b-nerve growth factor (NGF), stabilized with a carrier protein [bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS)], was mixed with a solution of a copolymer of e-caprolactone and ethyl ethylene phosphate (PCLEEP) in dichloromethane and electrospun as nanofibers.18b NGF was released via diffusion from the electrospun nanofibers for at least three months and retained its bioactivity. DNA has been encapsulated for potential therapeutic applications in gene therapy.19e It was found that plasmid DNA released directly from the electrospun scaffold was indeed intact, capable of transforming cells, and still encoded the alpha portion of the enzyme b-galactosidase. Filamentous bacterial viruses suspended in polymer solution were electrospun and found to remain viable when examined immediately and some time after electrospinning.19f,g (ii) Co-electrospinning of core–shell nanofibers Co-electrospinning of core–shell nanofibers allows one to diminish the direct contact of bioactive agents with the potentially dangerous solvents of the spinnable polymer. In such a process, the core contains an aqueous solution of a bioactive agent and shell contains a polymer in a non-aqueous solvent. Physical contact between the core aqueous solution containing bioactive agent and the shell polymer solution containing its solvents will be minimal, only at the core–shell interface. Co-electrospinning of core–shell fibers with coreand shell-containing aqueous solutions is a particular example of this method. In this case no potentially-detrimental solvents are involved in the system. Non-spinnable aqueous solutions of bioactive agents can be embedded in the core of the as-spun 2590 | J. Mater. Chem., 2007, 17, 2585–2599 core–shell nanofibers, whereas spinnable aqueous polymer solutions [for example, an aqueous solution of poly(vinyl alcohol), PVA] will create a shell. Core spinnability can be significantly enhanced by adding a small amount of a watersoluble and biocompatible polymer such as PEO. Following the general scheme of core–shell electrospinning, drugs (an antioxidant resveratrol and an antibiotic gentamycin sulfate) and proteins (BSA and lysozyme) were encapsulated in nanofiber cores surrounded by PCL solution shells with chloroform or DMF as solvents.18a,c Release profiles of drugs and proteins were studied experimentally. In particular, it was proven that lysozyme maintained its structure and was bioactive. Release of proteins from the core–shell nanofibers was accompanied by development of pores in the shell.18c Tailoring the shell thickness, the initial porosity and its variation with time should be a goal towards targeting an appropriate release rate and profile. Polymer choice (molecular weight and concentration in solution prior to co-electrospinning) in both the core and shell can be effectively used to control the release rate. In certain cases, a non-biocompatible polymer in the core might be the best choice for an appropriate release rate, whereas biocompatibility could be achieved by using a biocompatible polymer in the shell. It is well known that there are a broad range of application benefits from exploitation of biological species, e.g. enzymes, proteins, viruses and bacteria, in technical areas such as optical information technology, sensorics, catalysis, chemical synthesis or drug delivery.20 In the majority of cases these applications require that the biological objects are immobilized in specific carriers, and this has been achieved via adsorption, chemical binding or by encapsulation. Carbon nanotubes, zeolites, gold surfaces, polymer surfaces or hydrogels are examples for the spectrum of carrier systems used for immobilization. A major problem of this is that such types of immobilization tend to affect the specific structure (in particular the conformation) of the biological objects and, thus, their functions.21 A promising approach is based on fluid compartments in which the biological object will preserve its native conformation, its native functions and in which its rotational and translational degrees of freedom are not suppressed completely. This fluid compartment, in turn, will have to be immobilized within a solid carrier system. Such a carrier system should be structured on the nanoscale, since a rapid transport of matter into and out of the compartment is required for most of the applications introduced above. Nanostructured systems based on synthetic or natural polymers, and having the shape of core–shell fibers, have a lot to offer in this context. Nanofibers offer large specific surface areas and the number of natural or synthetic polymers available is huge, providing a multitude of materials appropriate for the preparation of the compartment. These organic materials can furthermore be functionalized by chemical, physical or via hybrid systems approaches within a broad range. Within this fluid compartment approach, the shell is not only responsible for keeping the compartments localized in a given place, but will also assume additional functions depending on the application. In drug release systems it will This journal is ß The Royal Society of Chemistry 2007 have to control the release kinetics, as mentioned above, and in protein-based sensor applications it should allow the compound(s) to be detected (i.e., the analyte) to diffuse to the proteins and out again into the environment. To obtain a rapid response, nanostructured core–shell fibers should be used with compartment diameters in the range of a few 100 nm (or even less) and with a shell thickness in the range of 200 to 500 nm. The particular architecture of the non-woven fiber assemblies offers additional advantages, as is obvious from extended Monte-Carlo simulations.22 The non-woven fiber assemblies are highly porous, with a porosity of about 90%. They can readily be permeated by viscous fluids, since all pores are accessible and the small sizes of the pores (as well as the corresponding high magnitude of the surfaces, as controlled by the nanofiber diameter) allow a rapid exchange of matter between the fluid reaction mixture and the compartments within the fibers. The core–shell fibers can be prepared as a non-woven fiber assembly or a set of parallel fibers or crossbars which are placed onto a porous solid support. Preparation of core–shell nanofiber systems containing localized fluid environments for functional materials and the approaches used are demonstrated in the following for core– shell nanofibers carrying the green fluorescent protein (GFP) as model system.5,23 It is composed of 238 amino acids and has a compact shape with a diameter of about 2.4 nm and a length of about 5 nm. These numbers are important with respect to a permanent immobilization in the fibers. A correlation exists for this protein between its conformation and its fluorescence. This correlation has been the subject of various investigations.24 Fluorescence is absent in the denaturated state and the denaturation can be caused by different environments such as, for instance, in the presence of urea. One advantage of GFP is that it transforms reversibly between the native and the denatured conformation if the surroundings are switched. This behaviour suggests that GFP can be used as model sensor system for sensor applications. The signal to be detected is the decay of the fluorescence as compounds such as, for instance, urea are present in the environment of the fiber arrangement and diffuse to the nanocontainers carrying GFP. The co-electrospun fibers were made by method (ii) from a 10 wt% polycarbonate solution (shell; Mw = 64 kDa, solvent: dichloromethane) and from a 150 mM GFP-solution (core). A distance of 15 cm between the die of the spinning set-up and the counter electrode was chosen along with a field of 1 kV cm21. In ref. 23 a DNA fragment encoding the eGFP was amplified by the polymerase chain reaction (PCR) from the vector pEGFP-N1 (Clontech, Heidelberg) and ligated into the expression vector pET22b (Novagen, Schwalbach/Ts.) to give plasmid pTK024. The synthetic oligonucleotides used for the PCR reactions contained the appropriate endonuclease restriction sites and encoded a few extra amino acids added to the termini of eGFP to give the following primary sequence: MCFFKDELGT-eGFP-GSRSHHHHHH (calculated mass 29.2 kDa). For the expression of the eGFP protein, E. coli BL21 cells were transformed with plasmid pTK024. A 6 mL overnight culture of the resulting strain in LB-medium containing 100 mg mL21 ampicillin was used to inoculate 600 mL of the same medium. Cells were grown at 37 uC and 250 rpm to an optical density (600 nm) of about 0.7. The This journal is ß The Royal Society of Chemistry 2007 temperature was then shifted to 30 uC and the expression was induced by the addition of isopropyl-b-D-thiogalactopyranoside to a final concentration of 0.4 mM. After 3–4 h, cells were pelleted by centrifugation, resuspended in wash buffer (50 mM Tris–HCl pH 8.0, 300 mM NaCl) with 5 mM imidazole, and frozen at 280 uC. For protein purification, cells were thawed on ice and disrupted in a French pressure cell. Insoluble cell material was pelleted by centrifugation for 15 min at 15 000 rpm in a Sorval SS-34 rotor. The soluble cell extract was loaded on a Ni2+–NTA agarose column (Qiagen), previously equilibrated with 10 column volumes of wash buffer with 5 mM imidazole. The subsequent washing steps were performed with 10 column volumes of wash buffer with 5 mM imidazole, 5 column volumes of wash buffer with 20 mM imidazole, and 3 column volumes of wash buffer with 40 mM imidazole. Proteins were eluted with elution buffer (50 mM Tris–HCl pH 8.0, 300 mM NaCl, 250 mM imidazole). The fractions containing the protein with .90% purity at an adequate concentration were pooled and dialyzed against PBS buffer (10 mM phosphate, 150 mM NaCl, pH 7.2) containing 2 mM DTT and 10% (v/v) glycerol and stored at 280 uC until further use. Fluorescence spectra were studied by an experimental set-up described previously in ref. 25. The fibers were characterized by a scanning electron microscope (Hitachi model 300), by a digital optical microscope (VHX 100, Keyence Comp.) and a fluorescence microscope (DMR Leica Comp.). The obvious advantage of co-electrospinning for the preparation of the biohybrid nanofibers mentioned above is that the core can be made from low viscosity fluids as well. A theory has been put forward which allows optimization of the co-electrospinning process in terms of the experimental set-up and the choice of the spinning parameters.13 It also allows an estimate of the electric and mechanical stresses acting, for instance, on biological objects subjected to entrainment in the core by co-electrospinning. An important feature of coelectrospinning (with respect to the incorporation of biological objects) is that the electric charges are practically only located at the outer surface. Therefore, the inner droplet in the twoliquid Taylor cone (Fig. 5) and, thus, biological objects dispersed in it, are not charged at all. They are only affected mechanically by the predominantly viscous stresses in the droplet. Predictions of these forces are already available from the theoretical investigations.13 Typical mechanical stresses which arise during electrospinning are of the order of 102 N m22. Biological macromolecules and biological structures can be destroyed by stresses of the order of 103–105 N m22 (ref. 19g and 26). The expectation, therefore, is that biological objects such as proteins, viruses or bacteria will not experience electrical stresses in co-electrospinning and that the viscous stresses can be adjusted to stay moderate. In any case, experiments show that biobased objects which have been subjected to co-electrospinning are still functional. Fig. 9a displays a microscope image of the core–shell fibers obtained by co-electrospinning and Fig. 9b the corresponding fluorescence microscope image. It is apparent that the GFP in the core is able to display fluorescence, and that nanocompartments are arranged in a regular fashion along the length of the core–shell fiber. J. Mater. Chem., 2007, 17, 2585–2599 | 2591 Fig. 9 (a) Core-shell nanofibers with GFP in the core compartments. (b) Fluorescence microscope image of the fibers. The shell is made from a 10 wt% polycarbonate solution and the core from a 150 mM GFP solution. To test the sensor functions of such core–shell fibers, they were brought into contact with a water environment containing urea. The observation was that the fluorescence signal (Fig. 10a) decayed as a function of the immersion time (Fig. 10b). A replacement of the urea solution by water causes the fluorescence to build up reversibly. The experimental results presented in this section have shown that the concept of immobilization of sensitive biological objects in fluid compartments within nanostructured polymer core–shell fibers works in principle. The approach sketched here used the model protein GFP in nanofiber carriers and the aim was a sensor application. The concept discussed here can be exploited in a variety of different architectures and applications. The incorporation of the GFP protein into porous membranes in a fluid environment where the pores are covered with a permeation layer is one example that is currently under study. IV Liquid transport in carbon and polymer nanotubes and encapsulation and orientation of particulates in confinements Encapsulation of liquids inside nanofibers and nanotubes implies, in many applications, their further transport along the confinement. The latter amounts, in fact, to micro- and nanofluidics, and attracts attention due to the peculiar transport phenomena and wide range of possible applications.27 Miniaturization results in lab-on-a-chip devices with smaller amounts of reagents and analytes, as well as higher 2592 | J. Mater. Chem., 2007, 17, 2585–2599 Fig. 10 (a) Fluorescence spectrum of the GFP within the core–shell fibers. (b) Decay of the fluorescence of the GFP within the core compartments in contact with a urea solution. reaction rates (if a device is used as a chemical reactor) due to the higher concentrations attainable. Microfabrication of microfluidic devices is typically complicated and expensive. Nanofluidics follows the same trend of miniaturization, however nanotube fabrication might be significantly simpler and cheaper. In this section we consider three types of carbon nanotubes (CNT): (a) traditional closed CNTs made of rolled graphene sheets,28 (b) open amorphous CNTs made by CVD inside pores, and (c) open turbostratic carbon nanotubes made via co-electrospinning. Traditional CNTs made of rolled graphene sheets are usually considered to be hydrophobic. Single-wall carbon nanotubes, SWCNTs, can be as narrow as 1 nm and are assumed to be atomically smooth. In general, water in large CNTs of 50–200 nm in diameter shows clearly distinguishable continuum-like patterns, while only in small CNTs (of the order of 2–5 nm or less) do continuum-like patterns disappear.29 In SWCNTs and the smallest multi-wall carbon nanotubes, MWCNTs, the combination of non-continuumlike behavior of the flowing medium and atomic smoothness and hydrophobicity of the wall results in transport rates several orders of magnitude higher than those which can be expected according to the classical fluid mechanical results (the Knudsen theory for rarefied gases and Poiseuille laminar flow for continuum fluids), as demonstrated by theoretical works based on molecular dynamics (MD) simulations30a,b and several experimental works.30c,d,e The most probable physical reasons for enhanced transport in these cases are related to This journal is ß The Royal Society of Chemistry 2007 alignment of water molecules due to hydrogen bonding in narrow confinements, and specular rather than diffusive reflections of transferring molecules from the atomically smooth walls. It is interesting that polymer nanopores with diameters of 16.8 nm probably do not possess the required atomic smoothness, as well as already being wide enough for continuum-like behavior of transferring fluid.30f As a result, gas diffusion in such nanopores follows the classical Knudsen theory, whereas water flow agrees with the Poiseuille law.30f The hydrothermal method of CNT synthesis results in water encapsulation inside the nanotube cavity.31 Water plugs surrounded by vapor in CNTs with diameters of the order of 100 nm have clearly expressed interfaces and behave in an almost continuum-like manner, even though they are strongly affected by intermolecular forces. The experiments31 showed that water plugs can be transferred along CNTs when observed using a transmission electron microscope. The reason for this is heating by the electron beam with the following vapor condensation due to intermolecular forces.32 Modelling32 revealed the pattern shown in Fig. 11. The results show that some material transport towards the cold end of CNT is indeed possible, and a liquid plug is seen growing there. The process is very slow and based on the model predictions—it is very difficult to say whether the whole liquid plug from the right-hand side end of the CNT in Fig. 11 can be transferred to the cold end. Open CVD-made nanotubes were brought into contact with such polar liquids as water, glycerol, ethylene glycol, ethanol, Fig. 11 Directional transport of liquid from the hot (right) to the cold (left) end of CNT. (a) The almost steady-state temperature field. Concentration fields are shown at t = (b) 0.3, (c) 0.4, (d) 0.5 (e) 0.6, where t is dimensionless time with the time scale being 102 s. A deep blue color in the concentration patterns corresponds to liquid, the lower concentration areas to vapor. E 2005 American Institute of Physics. Used with permission. This journal is ß The Royal Society of Chemistry 2007 Fig. 12 Video frame sequence of capillary filling of co-electrospun PCL tubes by silicon oil. E 2007 Wiley-VCH. Used with permission. tetrahydrofuran (THF) and 2-propanol alcohol, and such nonpolar liquids as cyclohexane, hexadecane, polydimethylsiloxane and fluoro-silicone, as well as with suspensions of several of these liquids laden with 50 nm diameter of fluorescent particles.33 Wettability-driven flows brought these fluids into CVD-nanotubes. Liquid evaporation at an open end of a CVD-nanotube can also contribute to the imbibition through the other end. The flows brought fluorescent particles into these CNTs which was visible through the transparent-tolight 15 nm-thick CNT walls. Co-electrospun hollow PCL nanotubes were filled with silicon oil which easily wets the PCL surface. Silicon oil was sucked by capillary forces through the porous shell.15 The meniscus propagation inside a hollow PCL tube recorded in ref. 15 is shown in Fig. 12. It is emphasized that, in contrast to regular capillary filling experiment where liquid is supplied at the entrance of the tube,33 in ref. 15 a silicon oil drop was placed on top of the micro-tube mat and the penetration was through the shell pores. As a result, the meniscus propagation laws recorded in ref. 15 and 33 significantly differ; namely, in ref. 33 it follows the Washburn equation, L(t) = (sa?cos h?t/2g)1/2, whereas in ref. 15 it does not (g, s and h are the liquid viscosity, surface tension and contact angle, a the tube inner cross-sectional radius, and L(t) is the meniscus position depending on time t). Electrospinning was used to entrain and encapsulate magnetic nanoparticles and carbon nanotubes in polymer nanofibers.34 The electrical conductivity and strength of the nanofibers are expected to be significantly improved when single- and multi-wall carbon nanotubes are incorporated in them. Attempts in this direction show that nanofibers containing both SWCNTs and MWCNTs can be electrospun from a polymer-based solution. Nanotubes were oriented and embedded inside nanofibers during electrospinning.34f,g Various colloidal particles, including titania nanoparticles, quantum dots and clay particles, were encapsulated in electrospun nanofibers.34j–o Flows in converging microchannels resemble that in the Taylor cone on top of the electrospun jet and represent themselves as an effective tool for reorientation and ordering of elongated micron-size particles. Theoretical predictions for the orientation–distribution probability density function in such converging flows and the corresponding experimental results on parallel arrangement of such elongated particles as J. Mater. Chem., 2007, 17, 2585–2599 | 2593 a Taylor–Couette apparatus,37a–d due to Dean vortices in curved channels,37e,f due to natural convection,37g and due to stationary d.c. streaming resulting from standing capillary waves.37h,i The circulatory vortices described in ref. 37 enhance particulate delivery to the interface, which builds a steep concentration gradient there. As a result, the particulate mass flux through the interface is enhanced, even though the diffusion coefficient stays low. None of the opportunities considered in ref. 37 are available in micro- and nanochannels. Given the fact that the particles (e.g., viruses) we are going to deal with could be uncharged and solvents could not contain any electrolytes, the temptation is to employ the dielectrophoretic force instead of vorticity to build steeper concentration gradients at the interface. This could be achieved by DQL, as is shown below. Fig. 13 Alignment of rod-like Bacillus magaterium bacteria in a converging sink/jet-like flow in a microchannel. E 2006 American Institute of Physics. Used with permission. CNTs and Bacillus magaterium bacteria (Fig. 13) can be found in ref. 34f and 35. V Microchannels as a dielectrophoretic quadrupole lens-on-a-chip for separation of viruses, nanoparticles and macromolecules Microchannel flows of encapsulated suspensions can be used for separation of particulates. For example, dielectrophoretic phenomena recently attracted significant attention in relation to the separation of uncharged cells, fine particles and macromolecules. A number of the previously published results were reviewed in ref. 36. In the present and following sections a new microscopic fluidic device is discussed, namely a dielectrophoretic quadrupole lens, DQL. This device should allow for an enhanced purification of liquids from suspended particles. In a biomedical context, we envision, for example, the purification of blood from viruses. The general design idea is supported by detailed calculations, which show that the device is feasible and effective. Purification of liquids from suspended submicron particulates is a tough engineering problem. Such particles being practically inertia-less, they follow the flow streamlines. For uncharged particles, the electrophoretic motion is out of scope, and the only realistic means of extraction are those related to their Brownian motion, i.e. diffusion. However, the particle diffusion coefficient Dp is extremely low (y1027 to 1025 cm2 s21), as compared to that of molecular compounds (y1021 cm2 s21). Therefore, the rate of diffusion processes towards interfaces or surfaces where the particles can be withdrawn/annihilated is extremely low, and mass transfer is rather ineffective. Recently, several attempts were made to intensify particulate mass transfer through interfaces between two immiscible liquids in macroscopic systems.37 In those cases, particles (proteins) were suspended in one of the liquids and should be removed to the other through the interface. In macroscopic two-liquid systems, mass transfer enhancement at the interface was achieved by means of secondary vortical circulatory flows emerging due to Taylor vortices in 2594 | J. Mater. Chem., 2007, 17, 2585–2599 VI DQL design If two immiscible liquids would be in contact over their joint interface with particles suspended in one of them (liquid 1), then due to diffusion the particles will pass to the other liquid (liquid 2). In a biomedical context, liquid 1 is, for example, blood, the particles are viruses, and liquid 2 could contain virus-specific antibody molecules which bind and kill the viruses. The diffusion process is, however, extremely slow, as explained in the previous section. The mass transfer process can be enhanced hydrodynamically using an impingement flow of liquids 1 and 2 (cf. Fig. 14), which will sustain a steep gradient of viruses near the interface, and keep the diffusion flux high enough even though the diffusion coefficient is low. The interfacial mass flux can be further dramatically enhanced employing dielectrophoresis. The micro-nanochannel walls depicted in Fig. 14 should be shaped as hyperbolas and be electrodes arranged in a quadrupole lens. They should be subjected to a high voltage with the electrode corresponding to the first quadrant in Fig. 14 (x . 0, y . 0) being, say, at the electric potential Q = B*. Following the subsequent quadrants in Fig. 14 clockwise, the potentials at the electrodes should be 2B*, B*, and 2B*. Moreover, the electric field should be ac to eliminate any electrophoretic effects related to charges on the particles and/or dissolved electrolytes if any. Therefore, Fig. 14 Sketch of DQL. This journal is ß The Royal Society of Chemistry 2007 B* = B0* exp(ivt), where v is a chosen (high) frequency. Volumetric Joule heating is not important in micro-nanochannels, since they are dominated by surface heat removal. Therefore, the system will effectively be isothermal even though a high electric power is applied. The hyperbolic shapes of the electrodes will facilitate a simple potential hydrodynamic flow field of the two impinging fluxes with blood (liquid 1) entering the device at y = ye and a decontaminant (liquid 2) at y = 2ye. The flow should be sustained by pumps. The hyperbolic shapes of the electrodes will also provide an electric field responsible for the dielectrophoretic force acting on the viruses. If the dielectric permittivity of blood is higher than that of the viruses, the latter will be pushed by the dielectrophoretic force towards the interface, which can dramatically enhance the virus transfer from blood to the decontaminant. An array of such devices could constitute a blood ‘‘dialysis’’ tool. Being attached to a patient, it can help decontaminate his/her blood from viruses, or sustain their concentration there under a certain level. Micro-devices similar to the one sketched in Fig. 14 could also be used for protein extraction and in many other processes requiring particulate removal from liquid 1. They may be manufactured on a chip. In the following sections we show that the dielectrophoretically-driven enhancement of the interfacial mass flux could be very significant under realistic conditions. The balance of forces acting on an inertia-less and uncharged particle is given by kB T+c 6pga vp {v zSd +E2 { ~0 c where the first term is the Stokes drag force, the second is the dielectrophoretic force of eqn (3), and the third term is the pseudo-force corresponding to diffusion; g is the solvent viscosity, vp and v the particle and solvent velocities, respectively, kB Boltzmann’s constant, T temperature and c the particle concentration. Then, the particle velocity can be expressed from eqn (6) as vp ~vzS1 +E2 {D F = Sd+E2 (3) 1 Sd ~ a3 ee Ref f g 2 (4) where Sd is given as where ee is the dielectric permittivity of solvent, a the particle radius, E = 2+Q is the electric field strength, the Clausius– Mossotti factor f is f~ ei {ee ei z2ee (5) and Re{} denotes the real part. Eqn (4) and the equations hereinafter are written using Gaussian (CGS) units. In eqn (5) ee* and ei* are the complex permittivities of solvent and particle, respectively. They are given as ee* = ee 2 i4pse/v and ei* = ei 2 i4psi/v, where ei is the particle dielectric permittivity, and se and si are the electric conductivities of solvent and particle, respectively; i is the imaginary unit. This journal is ß The Royal Society of Chemistry 2007 +c c (7) where D = kBT/(6pga) is the particle diffusion coefficient and S1 = Sd/(6pga). The mass balance of the particles is given by the following equation Lc z+:(cvp )~0 Lt (8) where t is time. Substituting eqn (7) in eqn (8), we arrive at the following dimensionless dielecrophoretic diffusion equation VII Dielectrophoretic diffusion equation Dielectric particles in electric fields polarize. The solvents surrounding them, also being dielectrics, polarize as well. If the dielectric permittivities of a particle and a solvent differ, electric Maxwell stresses should arise at the particle surface. In spatially non-uniform electric fields a non-zero net force (a non-zero stress integral over the particle surface) appears, which is called the dielectrophoretic force. Polarized particles could also be viewed as electric dipoles. In spatially nonuniform electric fields, such dipoles should inevitably experience a non-zero force, which is precisely the dielectrophoretic force F. It is given by the following expression38 (6) Lc z+:(cv)~+2 c{S+: c+E2 Lt (9) where S~ a2 e2 ee Ref f g 2 L 12pgDL2 (10) Eqn (9) is rendered dimensionless using the following scales: L for the coordinates x and y (say, L = ye), e/L - for Q and e/L2 - for E (where e is proton charge), L2/D - for t, and D/L - for v. Bars over dimensionless variables were dropped for brevity. Particle concentration c can be taken as dimensionless by definition or rendered dimensionless by a given characteristic concentration. The most interesting case corresponds to S , 0 (Re{f} , 0), where the solvent dielectric permittivity is higher than that of the particles. VIII Mass transfer in DQL The dimensionless electric potential in DQL is given by Q = Bxy (11) where B = B*L3/e. The solvent flow field is potential, i.e. given by the hydrodynamic potential W = (c/2)(x2 2 y2) with c being the rate of strain, which yields the following velocity components u and v corresponding to the Cartesian axes x and y u = cx, v = 2cy (12a,b) Note that the dimensionless rate of strain c is related with the dimensional rate c* as c = c*L2/D. J. Mater. Chem., 2007, 17, 2585–2599 | 2595 Eqn (11) and (12) allow calculation of the solvent velocity field v and the electric field strength E to be substituted into eqn (9). We consider a steady-state situation. In DQL, similarly to the other cases involving impinging flows,39 we expect that h2c/h2x ,, h2c/hy2and then, eqn (9) reduces to the following form ðczAÞx Lc Lc L2 c zð{czAÞy z2Ac~ 2 Lx Ly Ly (13) where A = 2B2S and the most interesting case corresponds to A , 0. Solutions of eqn (13) are subjected to the following boundary conditions y = 0 c = 0, y = 1 c = c0 (14a,b) which means that we assume liquid 2 to be able to immediately annihilate viruses entering it through the interface y = 0, ad virus concentration at the entrance into DQL is given as c0. Eqn (13) can be converted into the standard form L2 c Lc Lc zPðxÞy {RðxÞc~QðxÞ Ly2 Ly Lx (15) where P(x) = c 2 A, Q(x) = (c + A)x, R(x) = 2A (16) The solution of the problem (15)–(16) is searched in the form37h,39,40 ðx PðjÞ : dj W ðxÞ~2 QðjÞ o 2x 3{1=2 ð W ðjÞW ðxÞ e Z~y4 dj5 QðjÞ (17a c) o Substituting eqn (17) in (15), we obtain 2x 3 ð W ðjÞW ðxÞ d2 F Z dF e ~RðxÞF |4 z dj5 dZ 2 2 dZ QðjÞ K29M(1/2 + b/2, 1/2, f2/2)] (22) where K19 and K29 are the integration constants, b = 2A/(c 2 A), and M(?,?,?) is Kummer’s function.42 Eqn (17b) and (20) yield Z = [2(c 2 A)]1/2y and thus f = (c 2 A)1/2y, which yields cðx,yÞ~cð yÞ~ ðc AÞy2 c 3 ðc AÞy2 , , K1 yM exp cA 2 2 2 2 1 A 1 ðc AÞy , , zK2 M z 2 cA 2 2 (23) It is seen that the concentration field in DQL does not depend on x. The integration constants in eqn (23) are denoted as K1 and K2. They can be easily found using the solution (23) and the boundary conditions (14a,b). The result is cðx,yÞ~cð yÞ~ ðc AÞ 1 y2 c 3 ðc AÞy2 , , c0 exp yM cA 2 2 2 c 3 ðc A Þ , , =M cA 2 2 (24) Differentiating eqn (24), we find the concentration gradient at the interface Lc ðc AÞ c 3 ðc A Þ =M , , (25) ~c exp 0 Lyy~0 2 cA 2 2 Lc 2 c A 3=2c=ðcAÞ ~c0 pffiffiffi Cðc=ðc AÞÞ Lyy~0 2 p (18) o ðc AÞ j ‘n ðczAÞ x (19) Therefore, (26) where C(?) is the gamma function. The latter expression yields the flux of viruses towards liquid 2 as 2 c A 3=2c=ðcAÞ j~ c0 pffiffiffi Cðc=ðc AÞÞ 2 p Substituting eqn (16a,b) in eqn (17a), we find ðx F(f) = exp (2f2/2)[K19fM(1 + b/2, 3/ 2, f2/2) + For (c 2 A)/2 .. 1 eqn (25) yields c~F ðZÞ W ðjÞ W ðxÞ~2 Eqn (21) belongs to the family of the equations related to Whittaker’s equation.41 Its solution reads (27) where the flux j is rendered dimensionless by D/L. IX Numerical estimates: the efficacy of DQL eW ðjÞW ðxÞ 1 dj~ QðjÞ 2ðc{AÞ (20) o and eqn (18) reduces with the help of eqn (16c) and (20) to the following form d2 F dF 2A zf { F ~0 df ðc{AÞ df2 where f = Z/!2. 2596 | J. Mater. Chem., 2007, 17, 2585–2599 (21) The following parameters are used to estimate the efficacy of DQL: the length scale L = 1022 cm, the diffusion coefficient D = 1025 cm2 s21, the strain rate c* = 1021 s21, the virus radius a = 1025 cm, the blood viscosity g = 1022 g cm21 s21. The corresponding velocity scale D/L = 1023 cm s21 (c*L = 1023 cm s21 as well). The electric potential parameter B*L2 = 10–1000 V. Therefore, B*= (103–105)/3 g1/2 s21 cm23/2. The electric field strength which is of the order of B*L is of the order of 1–100 kV cm21, which can indeed be realized This journal is ß The Royal Society of Chemistry 2007 Fig. 15 Mass transfer enhancement in DQL. practically. The dielectric permittivity of blood is taken as ee = 81, whereas Re{f} = 21. The dimensionless groups corresponding to the abovementioned parameter values are c = 1 and A = 20.0486 to 486. The normalized particulate flux of eqn (27) J = j/[2c02/!p] is plotted in Fig. 15. Its value at A = 0 corresponds to the purely diffusion-convective transport and is equal to 0.7071. On the other hand, the values at A , 0 are higher due to the dielectrophoretic-related enhancement. At A = 210c = 210, a more than 100-fold increase in the virus flux through the liquid/liquid interface is achieved. At lower values of A (A , 210) the enhancement is even much higher. According to ref. 43, diffusion coefficients of some viruses can be as low as D = 1027 cm2 s21. With the other parameters being fixed, that corresponds to c = 100 and A = 24.86 to 48600. Then, for example at A = 210c = 2103, the relative enhancement (compared to the case of A = 0) will be more than 104-fold. The estimated values of the dielectrophoretic enhancement look promising and show that the efficacy of DQL may be quite high. Microfabrication methods make feasibility of DQL quite probable. In particular, turbostratic carbon nanotubes made via co-electrospinning might be used as building elements. X. Conclusion and perspectives Electrospinning and co-electrospinning will certainly continue to attract the attention of researchers in the fields of applied chemistry and material sciences, applied physics, polymer science and fluid mechanics, since they proved to be relatively simple and cheap methods for production of micro- and nanofibers and tubes. The basic physical mechanisms of these processes have already been elucidated, explained and described theoretically, however there are still numerous technological challenges to be faced on the way to high quality nanofibers and long nanotubes. These include tools for a better process control to guarantee robust production of uniform nanofibers and nanotubes with diameters about 100 nm, as well as functionalization of their outer and inner surfaces for a growing number of applications. For example, stimuli-responsive nanofibers and nanotubes could be This journal is ß The Royal Society of Chemistry 2007 envisioned based on polymer blends including such polymers as poly(N-isopropylacrylamide), PNIPAAm, which change their conformation in response to the surrounding temperature or pH level. PNIPAAm-based nanofibers and nanotubes can become a key element of self-regulating stimuli-responsive membranes and drug delivery devices. Nanofibers with embedded drugs, proteins and growth factors undoubtedly will be widely used for drug delivery, wound healing and in tissue engineering. Release mechanisms of many of these compounds are quite different from the simple Fickian diffusion models adopted in traditional controlled-release literature. This situation will almost certainly lead to a revision of our ideas on release mechanisms and incorporation of those of them which weren’t considered before. This will also be accompanied by development of novel types of nanofiber carriers with an extended release period (several months), without any initial burst of drug release. Major challenges to be addressed in the future concern electrospinning from the melt rather than from solutions, the extension of electrospinning to ceramic, metals and inorganic glasses, and finally a significant technical upscaling of the production rate, which is crucial for most of the potential applications envisioned for electrospun functional fibers. Nanotubes will definitely be used for storage of different compounds including such biological materials as bacteria, viruses, proteins and macromolecules (e.g., DNA). Then, understanding of the filling mechanisms becomes of the utmost importance. There are some experimental indications that wettability is not the only possible mechanism for filling of CVD and coelectrospun nanotubes. The goal is to achieve a relatively dense filling by high molecular weight compounds and it can probably be achieved using physical mechanisms stronger than wettability. New micro- and nanofluidic devices will almost certainly benefit from parallel bundles of centimeter-long nanotubes produced via co-electrospinning. They are relatively easy to handle and can be integrated in different ultrafiltration membranes, separators, ‘‘nanofluidic’’ interconnectors, labon-a-chip schemes and flow-through reactors. These devices can on one hand, guarantee the micro- and nanoconfinement required for a number of chemical and biological processes, and on the other hand, guarantee a relatively high throughput. All types of flow actuation in such nanotubes could be important: wettability-driven, pressure-driven and electricallydriven (electroosmosis and all its diffusion-mingled variants). A novel resistive-pulse DNA detection method44 presents itself for use in the carbon nanotubes produced via coelectrospinning for DNA detection. Parallel nanotube bundles of co-electrospun nanotubes can also become a key element of devices delivering several immiscible compounds into a cell, for example: two different types of growth factors. Dielectrophoteric virus separation in devices similar to DQL was reported in a recent paper45 and will definitely continue to attract attention. Acknowledgements We gratefully acknowledge the financial support by the VW Foundation (Programs-Komplexe Materialien: J. Mater. Chem., 2007, 17, 2585–2599 | 2597 Verbundprojekte der Natur-, Ingenieur-, und Biowissenschaften and the Project-Functional Composite Nanofibers by Co-electrospinning: Functional Nano-objects for Life Science). ALY gratefully acknowledges financial support by the National Science Foundation through grant NIRT CTS-0609062. The authors appreciate collaboration and contributions of their students and postdocs R. Avrahami, A. Bayer, A.V. Bazilevsky, L. Berkovici, R. Dersch, Y. Dror, N. Füchtjohann, E. Katz, S. N. Reznik, W. Salalha, Z. Sun and A. Theron, as well as collaboration with Doctors Y. Gogotsi and C. M. Megaridis. 15 16 17 18 References 1 (a) D. H. Reneker, A. L. Yarin, H. Fong and S. Koombhongse, J. Appl. Phys., 2000, 87, 4531; (b) A. L. Yarin, S. Koombhongse and D. H. Reneker, J. Appl. Phys., 2001, 89, 3018; (c) M. M. Hohman, M. Shin, G. Rutledge and M. P. Brenner, Phys. Fluids, 2001, 13, 2201; (d) M. M. Hohman, M. Shin, G. Rutledge and M. P. Brenner, Phys. 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