Bio-electrosprays: from bio-analytics to a generic tool for the health sciences

Electrosprays or electrospraying is a process by which an aerosol is generated between two charged electrodes. This aerosol generation methodology has been known for well over a century, and has undergone exploration in aerosol and materials sciences, to many other areas of research and development. In one such exploration, electrosprays were partnered with mass spectrometry for the accurate characterisation of molecules. This technology now widely referred to as electrospray ionisation mass spectrometry (ESI MS) significantly contributes to molecular analysis and cancer biology to name a few. In fact these findings were recognised by the Chemistry Nobel Committee in 2002, and have catapulted electrosprays to many areas of research and development. In this review, the author wishes to introduce and discuss another such recent discovery, where electrosprays have been investigated for directly handling living cells and whole organisms. Over the past few years these electrosprays now referred to as "bio-electrosprays" have undergone rigorous developmental studies both in terms of understanding all the associate physical, chemical and biological sciences for completely assessing their effects, if any on the direct handling of living biological materials. Therefore, the review will bring together all the work that has contributed to fully understanding that bio-electrosprays are an inert technology for directly handling living biological materials, while elucidating some unique features they possess over competing technologies. Hence, demonstrating this approach as a flexible methodology for a wide range of applications spanning bio-analytics, diagnostics to the possible creation of synthetic tissues, for repairing and replacing damaged/ageing tissues, to the targeted and controlled delivery of personalised medicine through experimental and/or medical cells and/or genes. Therefore, elucidating the far reaching ramifications bio-electrosprays have to our health sciences and well-being.     

Biosprayed spleen cells integrate and function in mouse models

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ), two non-contact direct cell handling approaches, have recently undergone rigorous scientific testing to assess whether cells retain chemical, physical and more importantly biological functions similarly to their unmanipulated counterparts. Previous in vitro validation of these two approaches has shown that they are inert for the direct handling and distributing of cells with great accuracy. In the present investigation we aim to validate, in vivo, that the spray techniques do not functionally or phenotypically alter splenic cells. By taking advantage of an adoptive transfer mouse model we demonstrated that the in vivo behaviour of treated cells is indistinguishable from unmanipulated cells following adoptive transfer into C57/BL6 mice. Indeed, sprayed cells survived and proliferated in response to antigen activation to similar levels observed in unmanipulated cells. In addition, in vivo sprayed cells displayed identical migratory characteristics to those observed in unmanipulated cells. Thus, demonstrating the inertness of these biosprays. Hence these biotechniques hold great potential for use in the development of three-dimensional cultures, tracking and monitoring cell-interactions and in vitro modelling of disease-states and therapeutics.     

Bio-electrosprayed living composite matrix implanted into mouse models

We show that composite de novo structures can be generated using bio-electrosprays. Mouse lung fibroblasts are bio-electrosprayed directly with a biopolymer to form cell-bearing matrices, which are viable even when implanted subcutaneously into murine hosts. Generated cell-bearing matrices are assessed in-vitro and found to undergo all expected cellular behaviour. Subsequent in-vivo studies demonstrate the implanted living matrices integrating as expected with the surrounding microenvironment. The in-vitro and in-vivo studies elucidate and validate the ability for either bio-electrosprays or cell electrospinning to form a desired living architecture for undergoing investigation for repairing, replacing and rejuvenating damaged and/or ageing tissues.     

Aerodynamically assisted bio-jetting of hematopoietic stem cells

The research reported in this communication demonstrates the emerging direct cell handling technology now widely referred to as aerodynamically assisted bio-jetting. This is a non-electric field driven approach which directly competes with bio-electrosprays. The technology in these investigations has been explored for the direct handling of live murine primary hematopoietic stem cells. The viability studies demonstrate the complete inertness of this technology for handling such cells for a wide range of applications in both basic biology and clinical medicine. Interestingly these studies pave the way for this technology to undergo development as a flow cell for utility as a sheathless cell most useful in flow cytometry.     

Fast speciation analysis of iodophenol compounds in river waters by capillary electrophoresis-inductively coupled plasma-mass spectrometry with off-line solid-phase microextraction

An analytical methodology for the fast separation and determination of iodophenol species in natural water samples was developed using capillary electrophoresis (CE) coupled to inductively coupled plasma-mass spectrometry (ICP-MS). Based on the element-specific and highly sensitive detection provided by ICP-MS, the methodology has been applied to the analysis of 2-iodophenol, 4-iodophenol, and 2,4,6-triiodophenol. The use of solid-phase microextraction (SPME), after proper optimization, improved the signal by a factor of 100 leading to detection limits in the sub microg.L(-1). Different desorption conditions of iodophenol compounds from the SPME microfiber were studied to achieve the optimum preconcentration factor and best analytical performance. Different CE conditions were studied to achieve complete baseline separation of iodophenols in short migration times. Three different CE buffer systems were evaluated using ICP-MS detection. A buffer solution containing 20 mmol.L(-1) 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) and an applied potential of +22 kV were finally selected leading to a maximum separation time of 6.6 min. A relative standard deviation (%RSD) of about 5.0% for ten consecutive determinations was obtained. Finally, the speciation methodology developed was utilized for the determination of iodophenol compounds in natural water samples.     

Phenolic constituents from the fruit juice of Flacourtia inermis

A chemical investigation of the fruit juice of Flacourtia inermis furnished five caffeoylquinic acid derivatives: methyl chlorogenate (1), methyl 5-O-caffeoylquinate (2), methyl 4-O-caffeoylquinate (3), n-butyl chlorogenate (4), n-butyl 5-O-caffeoylquinate (5) and a rare phenolic glucoside (rel)-6α-benzoyloxy-1α,2α-dihydroxy-5-oxocyclohex-3-enecarboxylic acid 2-(6-O-benzoyl-β-D-glucopyranosyloxy)-5-hydroxybenzyl ester (6), together with quinic acid (7) and malic acid (8). Compounds 1, 2, 4 and 5 showed strong radical scavenging properties towards the 2,2'-diphenyl-1-picrylhydrazyl radical.     

Identification and characterization of proanthocyanidins of 16 members of the Rhododendron genus (Ericaceae) by tandem LC-MS

The proanthocyanidins of the leaves of 16 taxa of the Rhododendron genus (Ericaceae) [Rhododendron 'Catawbiense Grandiflorum', Rhododendron 'Cunningham's White', Rhododendron smirnowii Trautv., Rhododendron calophytum Franch., Rhododendron dichroanthum ssp. scyphocalyx (Balf. f. & Forrest ) Cowan, Rhododendron micranthum Turcz., Rhododendron praevernum Hutch., Rhododendron ungernii Trautv., Rhododendron kaempferi Planch., Rhododendron degronianum ssp. heptamerum var. hondoense (Nakai ) H. Hara, Rhododendron fortunei Lindl., Rhododendron ponticum L., Rhododendron galactinum Balf. f. ex Tagg., Rhododendron oreotrephes W. W. Sm., Rhododendron brachycarpum ssp. brachycarpum D. Don ex G. Don, and Rhododendron insigne Hemsl. & E. H. Wilson ] were investigated qualitatively by liquid chromatography-mass spectrometry in series. Twenty-nine dimeric proanthocyanidins based on (epi)catechin and (epi)gallocatechin were detected and characterized on the basis of their unique fragmentation pattern in the negative ion mode tandem mass spectrometry spectra. All of them were extracted for the first time from these sources, and ten of them were not reported previously in nature. The position of the galloyl residue was assigned on the basis of the retro-Diels-Alder fragmentation and the dehydrated retro-Diels-Alder fragmentation; it resulted from the loss of gallic acid as a neutral loss in the negative ion mode. Furthermore, four caffeoylquinic acids, six p-coumaroylquinic acids, epigallocatechin, gallocatechin, catechin, epicatechin, epigallocatechin gallate, catechin gallate, epicatechin gallate, gallocatechin gallate, two quercetin-O-hexosides, quercetin-O-galloyl-hexoside, quercetin-O-pentoside, quercetin-O-rhamnoside, quercetin-O-pentoside-O-hexoside, quercetin-O-rhamnoside-O-hexoside, quercetin-O-feruloyl-hexoside, quercetin-O-(p-hydroxy)benzoyl-hexoside, taxifolin-O-pentoside, myricetin-O-rhamnoside, two myricetin-O-pentosides, three myricetin-O-hexosides, and two myricetin-O-galloyl-hexosides were detected and shown to possess characteristic tandem mass spectrometry spectra and were tentatively assigned on the basis of their retention time.     

Electrohydrodynamic atomization: an approach to growing continuous self-supporting polymeric fibers

The investigation presented in this paper illustrates a technique for growing in-situ polymerized networks, forming scaffold-like structures usually formed by means of electrospinning. The technique of jet atomization employing electrohydrodynamics is a manifestation of electrospinning. However, we show for the first time that using this technique where individual droplets are generated, a continuous self-supporting submicrometer web-like structure can be grown whereby fragments of the structure are delivered in the droplets and polymerize on the surface of the growing structure via polycondensation. The development of these growing fibers into web structures is a direct result of the processing route together with the excellent tailor-made cross-linking nature of the resin. An operational map is generated to identify a parametric space in which the stable cone-jet mode of electrohydrodynamic atomization prevails for generating the finest droplets. A statistical analysis on the formed fibers for a given time and electrospray condition is presented together with optical micrographs of the structure, which concludes the discussion in this paper.     

Electrospray self-assembly: An emerging jet-based route for directly forming nanoscaled structures

Electrosprays, a unique physical phenomenon has in the past decade or so been investigated for several applications spanning the physical and life sciences. Recently, these electrified jets were established for directly forming self-assembled structures with a range of non-conducting nanomaterials [Physica E 33 (2006) 398]. The current work demonstrates the ability to directly form functionalised building blocks in the nano-range with conducting nanoparticulates. In the remit of these investigations, we also studied whether particulate loading in suspension has an affect on the forming of these nanoscaled self-assemblies. Thus, these results have widespread promising implications for patterning a wide range of surface topographies either as near-annular islands—or track-like structures. Hence, such nano-assemblies formed by means of this top-down approach could be explored as a bottom-up methodology for encouraging cell migration to those architectures for forming cell patterns to nano-electronics, which are a few examples, respectively.