Bioimprint Mediated Label-Free Isolation of Pancreatic Tumor Cells from a Healthy Peripheral Blood Cell Population

New techniques are required for earlier diagnosis and response to treatment of pancreatic cancer. Here, a label-free approach is reported in which circulating pancreatic tumor cells are isolated from healthy peripheral blood cells via cell bioimprinting technology. The method involves pre-fabrication of pancreatic cell layers and sequential casting of cell surfaces with a series of custom-made resins to produce negative cell imprints. The imprint is functionalized with a combination of polymers to engineer weak attraction to the cells which is further amplified by the increased area of contact with the matching cells. A flow-through bioimprint chip is designed and tested for selectivity toward two pancreatic tumor cell lines, ASPC-1 and Mia-PaCa-2. Healthy human peripheral blood mononuclear cells (PBMCs) are spiked with pancreatic tumor cells at various concentrations. Bioimprints are designed for preferential retention of the matching pancreatic tumor cells and with respect to PBMCs. Tumor bioimprints are capable of capturing and concentrating pancreatic tumor cells from a mixed cell population with increased retention observed with the number of seedings. ASPC-1 bioimprints preferentially retain both types of pancreatic tumor cells. This technology could be relevant for the collection and interrogation of liquid biopsies, early detection, and relapse monitoring of pancreatic cancer patients

An(1)A_n^{(1)} Toda solitons and the dressing symmetry

We present an elementary derivation of the soliton-like solutions in the $A_n^{(1)}$ Toda models which is alternative to the previously used Hirota method. The solutions of the underlying linear problem corresponding to the N-solitons are calculated. This enables us to obtain explicit expression for the element which by dressing group action, produces a generic soliton solution. In the particular example of monosolitons we suggest a relation to the vertex operator formalism, previously used by Olive, Turok and Underwood. Our results can also be considered as generalization of the approach to the sine-Gordon solitons, proposed by Babelon and Bernard.Comment: 26 pages, Latex file, amssym.def needed, no figures; one new reference adde

Microfluidic device for the rapid coating of magnetic cells with polyelectrolytes

We demonstrate a rapid method of coating a layer of polymer onto magnetically modified yeast cells, so-called cyborg cells, in continuous flow within a microfluidic chamber. Laminar flow streams of polyelectrolyte and washing buffers were generated across the chamber, and the magnetic cells were deflected sequentially through the co-flowing streams via an external magnet, allowing polyelectrolyte deposition onto the cells immediately followed by the washing step, all in less than 90 s. This simple deposition technique shows promise for the functionalization of such cyborg cells for applications including bioelectronics, bioanalysis, and toxicity screening, while the addition of more reagent streams would enable the fabrication of multilayered capsules. © 2013 Elsevier B.V

Magnetically actuated particle-based procedures in continuous flow

We demonstrate a versatile multilaminar flow microfluidic device in which magnetic particles are used as mobile supports for performing two important applications, namely (i) a clinically relevant sandwich immunoassay, and (ii) polye-lectrolyte coating of templates towards the fabrication of microcapsules for drug delivery applications. Furthermore, we demonstrate the use of a different force, diamagnetic repulsion, for deflecting polystyrene particles through a reagent stream with a view to performing multilaminar flow studies on diamagnetic material such as polymer particles and cells

Microscreening toxicity system based on living magnetic yeast and gradient chips

There is an increasing demand for easy and cost-effective methods to screen the toxicological impact of the growing number of chemical mixtures being generated by industry. Such a screening method has been developed using viable, genetically modified green fluorescent protein (GFP) reporter yeast that was magnetically functionalised and held within a microfluidic device. The GFP reporter yeast was used to detect genotoxicity by monitoring the exposure of the cells to a well-known genotoxic chemical (methyl methane sulfonate, MMS). The cells were magnetised using biocompatible positively charged PAH-stabilised magnetic nanoparticles with diameters around 15 nm. Gradient mixing was utilised to simultaneously expose yeast to a range of concentrations of toxins, and the effective fluorescence emitted from the produced GFP was measured. The magnetically enhanced retention of the yeast cells, with their facile subsequent removal and reloading, allowed for very convenient and rapid toxicity screening of a wide range of chemicals. This is the first report showing magnetic yeast within microfluidic devices in a simple bioassay, with potential applications to other types of fluorescent reporter yeast in toxicological and biomedical research. The microfluidic chip offers a simple and low-cost screening test that can be automated to allow multiple uses (adapted to different cell types) of the device on a wide range of chemicals and concentrations. © 2010 Springer-Verlag

Direct measurements of the effects of salt and surfactant on interaction forces between colloidal particles at water-oil interfaces

The forces between colloidal particles at a decane-water interface, in the presence of low concentrations of a monovalent salt (NaCl) and of the surfactant sodium dodecylsulfate (SDS) in the aqueous subphase, have been studied using laser tweezers. In the absence of electrolyte and surfactant, particle interactions exhibit a long-range repulsion, yet the variation of the interaction for different particle pairs is found to be considerable. Averaging over several particle pairs was hence found to be necessary to obtain reliable assessment of the effects of salt and surfactant. It has previously been suggested that the repulsion is consistent with electrostatic interactions between a small number of dissociated charges in the oil phase, leading to a decay with distance to the power -4 and an absence of any effect of electrolyte concentration. However, the present work demonstrates that increasing the electrolyte concentration does yield, on average, a reduction of the magnitude of the interaction force with electrolyte concentration. This implies that charges on the water side also contribute significantly to the electrostatic interactions. An increase in the concentration of SDS leads to a similar decrease of the interaction force. Moreover the repulsion at fixed SDS concentrations decreases over longer times. Finally, measurements of three-body interactions provide insight into the anisotropic nature of the interactions. The unique time-dependent and anisotropic interactions between particles at the oil-water interface allow tailoring of the aggregation kinetics and structure of the suspension structure.Comment: Submitted to Langmui

Collective dynamics of colloids at fluid interfaces

The evolution of an initially prepared distribution of micron sized colloidal particles, trapped at a fluid interface and under the action of their mutual capillary attraction, is analyzed by using Brownian dynamics simulations. At a separation \lambda\ given by the capillary length of typically 1 mm, the distance dependence of this attraction exhibits a crossover from a logarithmic decay, formally analogous to two-dimensional gravity, to an exponential decay. We discuss in detail the adaption of a particle-mesh algorithm, as used in cosmological simulations to study structure formation due to gravitational collapse, to the present colloidal problem. These simulations confirm the predictions, as far as available, of a mean-field theory developed previously for this problem. The evolution is monitored by quantitative characteristics which are particularly sensitive to the formation of highly inhomogeneous structures. Upon increasing \lambda\ the dynamics show a smooth transition from the spinodal decomposition expected for a simple fluid with short-ranged attraction to the self-gravitational collapse scenario.Comment: 13 pages, 12 figures, revised, matches version accepted for publication in the European Physical Journal

Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

The osmotic virial coefficient $B_2$ of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that $B_2$ first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of $B_2$ is compared to experiments. Implications for protein crystallization are discussed.Comment: 43 pages, including 17 figure

From harmful Microcystis blooms to multi-functional core-double-shell microsphere bio-hydrochar materials

Harmful algal blooms (HABs) induced by eutrophication is becoming a serious global environmental problem affecting public health and aquatic ecological sustainability. A novel strategy for the utilization of biomass from HABs was developed by converting the algae cells into hollow mesoporous biohydrochar microspheres via hydrothermal carbonization method. The hollow microspheres were used as microreactors and carriers for constructing CaO2 core-mesoporous shell-CaO2 shell microspheres (OCRMs). The CaO2 shells could quickly increase dissolved oxygen to extremely anaerobic water in the initial 40 min until the CaO2 shells were consumed. The mesoporous shells continued to act as regulators restricting the release of oxygen from CaO2 cores. The oxygen-release time using OCRMs was 7 times longer than when directly using CaO2. More interestingly, OCRMs presented a high phosphate removal efficiency (95.6%) and prevented the pH of the solution from rising to high levels in comparison with directly adding CaO2 due to the OH− controlled-release effect of OCRMs. The distinct core-doubleshell micro/nanostructure endowed the OCRMs with triple functions for oxygen controlled-release, phosphorus removal and less impact on water pH. The study is to explore the possibility to prepare smarter bio-hydrochar materials by utilizing algal blooms