Aqueous two-phase systems: A viable platform in the manufacturing of biopharmaceuticals

The number of biotechnology-based pharmaceuticals in the late-stage pipeline has been increasing more than ever. As a result, there is an enhanced demand for more efficient and cost-effective processes. During the last years, the upstream technology for the production of biopharmaceuticals has been considerably improved. Continuous discoveries in molecular biology and genetics, combined with new advances in media and feed development, have significantly increased the production titres. In order to keep up this gain, it is now essential to design new, as well as to improve the existing downstream processes that remain an unresolved bottleneck. This review evaluates several alternatives to the currently established platforms for the downstream processing biopharmaceuticals, with main focus on aqueous two-phase extraction.     

Toward low-voltage dielectrophoresis-based microfluidic systems: A review

Dielectrophoretically driven microfluidic devices have demonstrated great applicability in biomedical engineering, diagnostic medicine, and biological research. One of the potential fields of application for this technology is in point-of-care (POC) devices, ideally allowing for portable, fully integrated, easy to use, low-cost diagnostic platforms. Two main approaches exist to induce dielectrophoresis (DEP) on suspended particles, that is, electrode-based DEP and insulator-based DEP, each featuring different advantages and disadvantages. However, a shared concern lies in the input voltage used to generate the electric field necessary for DEP to take place. Therefore, input voltage can determine portability of a microfluidic device. This review outlines the recent advances in reducing stimulation voltage requirements in DEP-driven microfluidics.     

pePC-SAFT: Modeling of polyelectrolyte systems 2. Aqueous two-phase systems

This work considers aqueous two-phase systems (ATPS) containing one polymer-polyelectrolyte as well as one salt. To model the liquid-liquid equilibria (LLE) of these systems, the recently presented model pePC-SAFT has been employed. ATPS containing poly(acrylic acid) of different degrees of neutralization or poly(vinyl pyrrolidone), respectively, were considered. The binary interaction parameters used between water-poly(acrylic acid) and water-poly(vinyl pyrrolidone) were adjusted to vapor-liquid equilibrium (VLE) data of these systems. ATPS consisting of poly(vinyl pyrrolidone)-water-sodium sulfate were predicted as function of temperature as well as of molar mass of the polymer. For poly(acrylic acid) systems, ATPS were predicted as function of charge density (degree of neutralization) for different types of salt. For these calculations, the polyelectrolyte model parameters were determined from the non-charged polymer whereas the effect of increasing charge density has been purely predicted by the model. Using this approach, it is possible to predict the shrinking of the liquid-liquid equilibrium region with increasing charging of the polyelectrolyte.     

Natural-convective instability of electrochemical systems: A review

Basic theoretical and experimental results of research into natural-convective instability of electrochemical systems are considered.     

Nanoparticle-based assays in automated flow systems: A review

Nanoparticles (NPs) exhibit a number of distinctive and entrancing properties that explain their ever increasing application in analytical chemistry, mainly as chemosensors, signaling tags, catalysts, analytical signal enhancers, reactive species generators, analyte recognition and scavenging/separation entities.     

Unconventional TLC systems in lipophilicity determination: A review

ABSTRACT

This review focuses on four unusual thin-layer chromatography (TLC) approaches for the determination of lipophilicity: (1) the use of medium-polar stationary phases: CN, NH₂, and DIOL instead of RP plates, together with water-based mobile phase; (2) the use of silica gel in a typical normal-phase manner and treating extrapolated retention indices as the “reversed lipophilicity”; (3) the use of oil impregnated silica gel in the reversed-phase manner; and (4) the use of salting-out mobile phases. The chromatographic indices obtained in these systems are numerously reported as well correlated with lipophilicity and they are an interesting alternative to classical RP systems approaches.     

Aqueous two-phase systems for protein separation: a perspective

Aqueous two-phase systems (ATPS) that are formed by mixing a polymer (usually polyethylene glycol, PEG) and a salt (e.g. phosphate, sulphate or citrate) or two polymers and water can be effectively used for the separation and purification of proteins. The partitioning between both phases is dependent on the surface properties of the proteins and on the properties of the two phase system. The mechanism of partitioning is complex and not very easy to predict but, as this review paper shows, some very clear trends can be established. Hydrophobicity is the main determinant in the partitioning of proteins and can be measured in many different ways. The two methods that are more attractive, depending on the ATPS used (PEG/salt, PEG/polymer), are those that consider the 3-D structure and the hydrophobicity of AA on the surface and the one based on precipitation with ammonium sulphate (parameter 1/m*). The effect of charge has a relatively small effect on the partitioning of proteins in PEG/salt systems but is more important in PEG/dextran systems. Protein concentration has an important effect on the partitioning of proteins in ATPS. This depends on the higher levels of solubility of the protein in each of the phases and hence the partitioning observed at low protein concentrations can be very different to that observed at high concentrations. In virtually all cases the partition coefficient is constant at low protein concentration (true partitioning) and changes to a different constant value at a high overall protein concentration. Furthermore, true partitioning behavior, which is independent of the protein concentration, only occurs at relatively low protein concentration. As the concentration of a protein exceeds relatively low values, precipitation at the interface and in suspension can be observed. This protein precipitate is in equilibrium with the protein solubilized in each of the phases. Regarding the effect of protein molecular weight, no clear trend of the effect on partitioning has been found, apart from PEG/dextran systems where proteins with higher molecular weights partitioned more readily to the bottom phase. Bioaffinity has been shown in many cases to have an important effect on the partitioning of proteins. The practical application of ATPS has been demonstrated in many cases including a number of industrial applications with excellent levels of purity and yield. This separation and purification has also been successfully used for the separation of virus and virus-like particles.     

Biopolymer based nanomaterials in drug delivery systems: A review

Drug delivery systems (DDS) are used to achieve a higher therapeutic effects of a pharmaceutical drug or natural compound in a specific diseased site with minimal toxicological effect and these systems consists of liposomes, microspheres, gels, prodrugs and many. Nanotechnology is a rapidly developing multi-disciplinary science that ensures the fabrication of the polymers to nanometer scale for various medical applications. Uses of biopolymers in DDS ensure the biocompatibility, biodegradability and low immunogenicity over the synthetic ones. Biopolymers such as silk fibroins, collagen, gelatin, albumin, starch, cellulose and chitosan can be easily made into suspension that serve as delivery vehicles for both macro and mini drug molecules. There are various methods such as supercritical fluid extraction, desolvation, electrospraying, spray-drying, layer-by-layer self-assembly, freeze-drying and microemulsion introduced to make these DDS. This drug carrier systems enhance the drug delivery actively and can be used in ocular, transdermal, dental or intranasal delivery systems. This review describes the new trends in nanomaterials based drug delivery systems mainly using biopolymers such as proteins (silk fibroin, collagen, gelatin and albumin) and polysaccharides (chitosan, alginate, cellulose and starch).     

Polymer-drug conjugates as inhalable drug delivery systems: A review

Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetic profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety in the lungs, which is closely linked to lung retention times. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments for several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps.     

Aqueous two-phase systems in biochemical recovery

The design and application of aqueous two-phase systems for recovery of proteins is reviewed. Reference is made to the properties of polymers and salt forming the systems and their influence on phase separation and partition. The properties of systems important for the design of purification strategies are discussed in relation to the surface properties of proteins. Strategies for the modification of systems for bioaffinity partition are considered including the choice of carrier in terms of molecular type and properties, or by particulate addition. Finally, the scaleup of partition is considered, and the reasons for currently limited adoption at larger scales are elucidated.     

Aqueous organic and redox-mediated redox flow batteries: a review

Redox flow batteries (RFBs) are among the most investigated technologies for large-scale energy storage applications. Since the first commercialization of all-vanadium RFB (in the early 90s), the technology has evolved towards the development of new systems. This review focuses on three innovative concepts including aqueous organic RFB (AO-RFB), dual-circuit RFB and redox solid booster–based RFB. We will highlight the recent advances in the last five years and discuss the main challenges encountered. Particularly, we focused on the use of redox-mediated process to reach higher energy density than conventional RFB.     

Advanced drug delivery systems: Nanotechnology of health design A review

Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.     

The nanomaterials and recent progress in biosensing systems: A review

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Aqueous biphasic systems involving alkylsulfate-based ionic liquids

The specific effects of K₃PO₄, K₂CO₃, Na₂CO₃, and (NH₄)₂SO₄, as high charge-density inorganic salts and thus inducers of the formation of aqueous biphasic systems (ABS) containing several ethyl-methylimidazolium alkylsulfate ionic liquids, C₂MIM C_nSO₄ (n = 2, 4, 6, or 8), have been assessed at T = 298.15 K. The results are analyzed in the light of the Hofmeister series. The influence of different alkyl chain lengths in the anion, together with the ability of the selected inorganic salts to induce the formation of ABS, is discussed. Phase diagrams have been determined through turbidimetry, including tie lines assignments from mass phase ratios according to the lever – arm rule. The Merchuck equation was satisfactorily used to correlate the solubility curve.     

Temporal gradients in microfluidic systems to probe cellular dynamics: A review

Microfluidic devices have found a unique place in cellular studies due to the ease of fabrication, their ability to provide long-term culture, or the seamless integration of downstream measurements into the devices. The accurate and precise control of fluid flows also allows unique stimulant profiles to be applied to cells that have been difficult to perform with conventional devices. In this review, we describe and provide examples of microfluidic systems that have been used to generate temporal gradients of stimulants, such as waveforms or pulses, and how these profiles have been used to produce biological insights into mammalian cells that are not typically revealed under static concentration gradients. We also discuss the inherent analytical challenges associated with producing and maintaining temporal gradients in these devices.     

3D skin models along with skin-on-a-chip systems: A critical review

Skin is the largest organ in human body, and it plays an important role in regulating physiological microenvironments and acts as a barrier to protect human body from harmful intrusions. The demand for fully functional skin models(also called skin equivalents, SE) in an in-vivo mimicking culturing microenvironment has been increased dramatically due to the fast development in skin disease treatments and skin care products. Owing to the emerging of the concept and technology of organ-on-chips alo...     

A review on polysiloxane-immobilized ligand systems: Synthesis, characterization and applications

The immobilized silica gel ligand systems made by modification of silica surfaces have been briefly summarized. Short background was described based on the synthesis methods and their applications. In this review more attention towards the functionalized polysiloxane xerogels and their postmodification has been given. Polysiloxane-immobilized ligand systems bearing organofunctionalized ligand groups of general formula P-(CH₂)₃-X (where P represents a three-dimensional silica like network-matrix and X is an organofunctional group) were prepared through the sol-gel process by hydrolytic polycondensation of Si(OR)₄ and the appropriate silane coupling agent (RO)₃Si(CH₂)₃X (where R is an alkyl group, e.g CH₃ or C₂H₅). There are many other immobilized ligand systems, which were prepared by treatment of post-polysiloxane precursors with an appropriate organofunctional ligand. Variety of functionalized materials ranging from simple up to macrocyclic immobilized ligand systems were prepared and well characterized. These materials have the advantage over the functionalized silica, as they can be prepared using different molar ratios of Si(OR)₄ and (RO)₃Si(CH₂)₃X silane agents, and therefore their metal uptake capacities can be altered. A mixture of two different ligand groups can also be achieved on the same matrix. Analytical and environmental applications of these materials have been reported including extraction, separation and preconcentration of metal ions. A variety of physical chemistry techniques that were employed to characterize the surface and the bulk of the immobilized systems were reported. These included high-resolution solid-state nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR).     

Aqueous two-phase systems containing N-vinylpyrrolidone: Experimental results and correlation/prediction

Experimental results are presented for the liquid–liquid equilibrium of a ternary system (N-vinylpyrrolidone + sodium sulfate + water) and three quaternary systems composed of (N-vinylpyrrolidone + poly(vinylpyrrolidone) + sodium sulfate + water) at 25 °C. The quaternary systems differ in the number averaged molecular mass of the poly(vinylpyrrolidones). That molecular mass was between about 4 000 and 140 000. The experimental results are described with a semi-empirical model (VERS model) for the excess Gibbs energy.     

Generator-collector double electrode systems: a review

A variety of generator-collector systems are reviewed, from the original rotating ring-disc electrodes developed in the 1950s, to very recent developments using new geometries and microelectrodes. An overview of both theoretical and experimental aspects are given, and the power of these double electrode systems in analytical electrochemistry is illustrated with a range of applications.