Publications

by Keyword: Separation


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Quiliano, Miguel, Pabón, Adriana, Moles, Ernest, Bonilla-Ramirez, Leonardo, Fabing, Isabelle, Fong, Kim Y., Nieto-Aco, Diego A., Wright, David W., Pizarro, Juan C., Vettorazzi, Ariane, López de Cerain, Adela, Deharo, Eric, Fernàndez-Busquets, Xavier, Garavito, Giovanny, Aldana, Ignacio, Galiano, Silvia, (2018). Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery European Journal of Medicinal Chemistry 152, 489-514

Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70–73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70–73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50s < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC50s < 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.

Keywords: Antiplasmodial, Antimalarial, Arylamino alcohol, Multi-stage activity, Hsp90, Enantiomer separation


O'Neill, R., McCarthy, H. O., Montufar, E. B., Ginebra, M. P., Wilson, D. I., Lennon, A., Dunne, N., (2017). Critical review: Injectability of calcium phosphate pastes and cements Acta Biomaterialia 50, 1-19

Calcium phosphate cements (CPC) have seen clinical success in many dental and orthopaedic applications in recent years. The properties of CPC essential for clinical success are reviewed in this article, which includes properties of the set cement (e.g. bioresorbability, biocompatibility, porosity and mechanical properties) and unset cement (e.g. setting time, cohesion, flow properties and ease of delivery to the surgical site). Emphasis is on the delivery of calcium phosphate (CaP) pastes and CPC, in particular the occurrence of separation of the liquid and solid components of the pastes and cements during injection; and established methods to reduce this phase separation. In addition a review of phase separation mechanisms observed during the extrusion of other biphasic paste systems and the theoretical models used to describe these mechanisms are discussed. Statement of Significance Occurrence of phase separation of calcium phosphate pastes and cements during injection limits their full exploitation as a bone substitute in minimally invasive surgical applications. Due to lack of theoretical understanding of the phase separation mechanism(s), optimisation of an injectable CPC that satisfies clinical requirements has proven difficult. However, phase separation of pastes during delivery has been the focus across several research fields. Therefore in addition to a review of methods to reduce phase separation of CPC and the associated constraints, a review of phase separation mechanisms observed during extrusion of other pastes and the theoretical models used to describe these mechanisms is presented. It is anticipated this review will benefit future attempts to develop injectable calcium phosphate based systems.

Keywords: Bone cements, Calcium phosphates, Injectability, Material properties, Phase separation


Oller-Moreno, S., Singla-Buxarrais, G., Jiménez-Soto, J. M., Pardo, Antonio, Garrido-Delgado, R., Arce, L., Marco, Santiago, (2015). Sliding window multi-curve resolution: Application to gas chromatography - Ion Mobility Spectrometry Sensors and Actuators B: Chemical 15th International Meeting on Chemical Sensors , Elsevier (Buenos Aires, Argentina) 217, 13-21

Abstract Blind Source Separation (BSS) techniques aim to extract a set of source signals from a measured mixture in an unsupervised manner. In the chemical instrumentation domain source signals typically refer to time-varying analyte concentrations, while the measured mixture is the set of observed spectra. Several techniques exist to perform BSS on Ion Mobility Spectrometry, being Simple-to-use interactive self-modeling mixture analysis (SIMPLISMA) and Multivariate Curve Resolution (MCR) the most commonly used. The addition of a multi-capillary gas chromatography column using the ion mobility spectrometer as detector has been proposed in the past to increase chemical resolution. Short chromatography times lead to high levels of co-elution, and ion mobility spectra are key to resolve them. For the first time, BSS techniques are used to deconvolve samples of the gas chromatography - ion mobility spectrometry tandem. We propose a method to extract spectra and concentration profiles based on the application of MCR in a sliding window. Our results provide clear concentration profiles and pure spectra, resolving peaks that were not detected by the conventional use of MCR. The proposed technique could also be applied to other hyphenated instruments with similar strong co-elutions.

Keywords: Blind Source Separation, Multivariate Curve Resolution, Ion Mobility Spectrometry, Gas Chromatography, Hyphenated instrumentation, SIMPLISMA, co-elution


Ivon Rodriguez-Villarreal, Angeles, Tarn, Mark D., Madden, Leigh A., Lutz, Julia B., Greenman, John, Samitier, Josep, Pamme, Nicole, (2011). Flow focussing of particles and cells based on their intrinsic properties using a simple diamagnetic repulsion setup Lab on a Chip 11, (7), 1240-1248

The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.

Keywords: Feeble magnetic substances, On-chip, Blood-cells, Microfluidic device, Separation, Field, Levitation, Magnetophoresis, Fractionation, Nanoparticles


Jaramillo, M. D., Torrents, E., Martinez-Duarte, R., Madou, M. J., Juarez, A., (2010). On-line separation of bacterial cells by carbon-electrode dielectrophoresis Electrophoresis , 31, (17), 2921-2928

Dielectrophoresis (DEP) represents a powerful approach to manipulate and study living cells. Hitherto, several approaches have used 2-D DEP chips. With the aim to increase sample volume, in this study we used a 3-D carbon-electrode DEP chip to trap and release bacterial cells. A continuous flow was used to plug an Escherichia coli cell suspension first, to retain cells by positive DEP, and thereafter to recover them by washing with peptone water washing solution. This approach allows one not only to analyze DEP behavior of living cells within the chip, but also to further recover fractions containing DEP-trapped cells. Bacterial concentration and flow rate appeared as critical parameters influencing the separation capacity of the chip. Evidence is presented demonstrating that the setup developed in this study can be used to separate different types of bacterial cells.

Keywords: Bacteria, Carbon electrode, Dielectrophoresis, E. coli, Separation


Pomareda, V., Calvo, D., Pardo, A., Marco, S., (2010). Hard modeling multivariate curve resolution using LASSO: Application to ion mobility spectra Chemometrics and Intelligent Laboratory Systems , 104, (2), 318-332

Multivariate Curve Resolution (MCR) aims to blindly recover the concentration profile and the source spectra without any prior supervised calibration step. It is well known that imposing additional constraints like positiveness, closure and others may improve the quality of the solution. When a physico-chemical model of the process is known, this can be also introduced constraining even more the solution. In this paper, we apply MCR to Ion Mobility Spectra. Since instrumental models suggest that peaks are of Gaussian shape with a width depending on the instrument resolution, we introduce that each source is characterized by a linear superposition of Gaussian peaks of fixed spread. We also prove that this model is able to fit wider peaks departing from pure Gaussian shape. Instead of introducing a non-linear Gaussian peak fitting, we use a very dense model and rely on a least square solver with L1-norm regularization to obtain a sparse solution. This is accomplished via Least Absolute Shrinkage and Selection Operator (LASSO). Results provide nicely resolved concentration profiles and spectra improving the results of the basic MCR solution.

Keywords: Blind source separation, Ion mobility spectrometry, Multivariate curve resolution, Sparse solution, Non negative matrix factorization


Marco, S., Pomareda, V., Pardo, A., Kessler, M., Goebel, J., Mueller, G., (2009). Blind source separation for ion mobility spectra Olfaction and Electronic Nose: Proceedings of the 13th International Symposium on Olfaction and Electronic Nose 13th International Symposium on Olfaction and the Electronic Nose (ed. Pardo, M., Sberveglieri, G.), Amer Inst Physics (Brescia, Italy) 1137, 551-553

Miniaturization is a powerful trend for smart chemical instrumentation in a diversity of applications.. It is know that miniaturization in IMS leads to a degradation of the system characteristics. For the present work, we are interested in signal processing solutions to mitigate limitations introduced by limited drift tube length that basically involve a loss of chemical selectivity. While blind source separation techniques (BSS) are popular in other domains, their application for smart chemical instrumentation is limited. However, in some conditions, basically linearity, BSS may fully recover the concentration time evolution and the pure spectra with few underlying hypothesis. This is extremely helpful in conditions where non-expected chemical interferents may appear, or unwanted perturbations may pollute the spectra. SIMPLISMA has been advocated by Harrington et al. in several papers. However, more modem methods of BSS for bilinear decomposition with the restriction of positiveness have appeared in the last decade. In order to explore and compare the performances of those methods a series of experiments were performed.

Keywords: Ion Mobility Spectrometry (IMS), Blind Source Separation (BSS), Multivariate Analysis, SIMPLISMA, MCR, Non-Negative Matrix Factorization (NMF)


Castellarnau, Marc, Errachid, Abdelhamid, Madrid, Cristina, Juárez, Antonio, Samitier, Josep, (2006). Dielectrophoresis as a tool to characterize and differentiate isogenic mutants of Escherichia coli Biophysical Journal , 91, (10), 3937-3945

In this study we report on an experimental method based on dielectrophoretic analysis to identify changes in four Escherichia coli isogenic strains that differed exclusively in one mutant allele. The dielectrophoretic properties of wild-type cells were compared to those of hns, hha, and hha hns mutant derivatives. The hns and hha genes code respectively for the global regulators Hha and H-NS. The Hha and H-NS proteins modulate gene expression in Escherichia coli and other Gram negative bacteria. Mutations in either hha or hns genes result in a pleiotropic phenotype. A two-shell prolate ellipsoidal model has been used to fit the experimental data, obtained from dielectrophoresis measurements, and to study the differences in the dielectric properties of the bacterial strains. The experimental results show that the mutant genotype can be predicted from the dielectrophoretic analysis of the corresponding cultures, opening the way to the development of microdevices for specific identification. Therefore, this study shows that dielectrophoresis can be a valuable tool to study bacterial populations which, although apparently homogeneous, may present phenotypic variability.

Keywords: H-NS, Dielectric behaviour, Hemolysin genes, Cells, Separation, Expression, Proteins, HHA, Electrorotation, Polarization